GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
Q16584	P46734	1	phosphorylation	up-regulates activity	0.492	Immunoprecipitated mlk-3 catalyzed the phosphorylation of sek1 in vitro, and co-transfected mlk-3 induced phosphorylation of sek1 and mkk3 at sites required for activation, suggesting direct regulation of these protein kinases.	SIGNOR-45788
O00308	Q9H074	1	ubiquitination	down-regulates quantity by destabilization	0.332	Here, we show that the E6AP carboxyl terminus (HECT)-type ubiquitin ligase WW domain-containing protein 2 (WWP2), a homolog of the HECT-type ubiquitin ligase WWP1, interacts with and targets Paip1 for ubiquitination and proteasomal degradation.	SIGNOR-272842
P63096	P09619	0	phosphorylation	up-regulates activity	0.2	RTKs directly phosphorylate Gαi on Y154, 155, and Y320.	SIGNOR-277232
Q9HC62	Q15418	0	phosphorylation	down-regulates activity	0.2	Here, we determined that d-flow activated the serine/threonine kinase p90RSK, which subsequently phosphorylated threonine 368 (T368) of SENP2. T368 phosphorylation promoted nuclear export of SENP2, leading to downregulation of eNOS expression and upregulation of proinflammatory adhesion molecule expression and apoptosis.	SIGNOR-273839
Q13555	P42261	1	phosphorylation	up-regulates activity	0.63	In this study, CaM-kinase II enhanced kainate currents of expressed glutamate receptor 6 in 293 cells and of wild-type glutamate receptor 1, but not the Ser-627 to Ala mutant, in Xenopus oocytes. \| This CaM-kinase II regulatory phosphorylation site is conserved in all AMPA/kainate-type glutamate receptors, and its phosphorylation may be important in enhancing postsynaptic responsiveness as occurs during synaptic plasticity.	SIGNOR-250697
P12931	P61978	1	phosphorylation	down-regulates	0.603	We show that hnrnp k and the c-src kinase specifically interact with each other, leading to c-src activation and tyrosine phosphorylation of hnrnp k in vivo and in vitro. c-src-mediated phosphorylation reversibly inhibits the binding of hnrnp k to the differentiation control element (dice) of the lox mrna 3' untranslated region in vitro and specifically derepresses the translation of dice-bearing mrnas in vivo.We confirmed that tyr 230, 234, 236, and 380 are phosphorylated and identified two additional targets of c-src, tyr 72 and tyr 225 (data not shown).	SIGNOR-88911
Q03112	P24941	0	phosphorylation	up-regulates activity	0.296	The motif harbouring S436 is a target of CDK2 and CDK3 kinases, which interacted with EVI1-WT. The methyltransferase DNMT3A bound preferentially to EVI1-WT compared with EVI1-S436A, and a hypomethylated cell population associated by EVI1-WT expression in murine haematopoietic progenitors is not maintained with EVI1-S436A.	SIGNOR-273426
P48729	P55957	1	phosphorylation	up-regulates activity	0.286	Here we report that Bid is phosphorylated by casein kinase I (CKI) and casein kinase II (CKII). Inhibition of CKI and CKII accelerated Fas-mediated apoptosis and Bid cleavage, whereas hyperactivity of the kinases delayed apoptosis. \| These results suggest that residues S61, S64, and to a much lesser extent T58 are sites of phosphorylation of Bid.	SIGNOR-250785
Q05397	P09769	0	phosphorylation	up-regulates	0.552	Phosphorylated on tyrosine residues upon activation. Phosphorylation at tyr-925 is important for interaction with grb2 and depends on the complex formation between fak and the src-kinase fgr.	SIGNOR-94405
Q8N257	Q14493	0	translation regulation	up-regulates quantity by expression	0.2	Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA\|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control.	SIGNOR-265388
P24941	P78317	1	phosphorylation	up-regulates activity	0.2	Here we reported that CDK2 could phosphorylate RNF4 on T26 and T112 and enhance RNF4 E3 ligase activity, which is important for MDC1 degradation and proper HR repair during S phase.	SIGNOR-276900
P17655	Q15078	1	cleavage	up-regulates activity	0.565	Calpains also modulate the activity of CDK5. Physiologically, CDK 5 is activated by p35 and its cleaved product p25. The latter has a longer half life than p35 and therefore it is a more potent activator of CDK5. The cleavage of p35 to p25 is mediated by calpain	SIGNOR-251610
Q9H3Y6	P45985	1	phosphorylation	down-regulates activity	0.2	SRMS directly phosphorylates MKK4 and inhibits MKK4-JNK-c-Jun activation upon platinum treatment. Platinum treatment-induced ROS activates SRMS, which inhibits MKK4 kinase activity by directly phosphorylating MKK4 at Y269 and Y307, and consequently attenuates MKK4-JNK activation.	SIGNOR-277902
P06493	P18031	1	phosphorylation	up-regulates activity	0.502	Cdk1-cyclin B1 directly phosphorylates PTP1B at serine 386 in a kinase assay. Recombinant Plk1 phosphorylates PTP1B on serine 286 and 393 in vitro, however, it requires a priming phosphorylation by Cdk1 at serine 386 highlighting a novel co-operation between Cdk1 and Plk1 in the regulation of PTP1B.\|Finally, phosphorylation on serine 286 enhanced PTP1B phosphatase activity.	SIGNOR-272970
Q15831	P17612	0	phosphorylation	up-regulates activity	0.502	Phosphorylation of the protein kinase mutated in Peutz-Jeghers cancer syndrome, LKB1/STK11, at Ser431 by p90(RSK) and cAMP-dependent protein kinase, but not its farnesylation at Cys(433), is essential for LKB1 to suppress cell growth.	SIGNOR-250055
O60331	P12931	0	phosphorylation	up-regulates	0.285	Phosphorylation by src of the tyrosine adjacent to s650 (y649 in human pipki gamma) was shown to enhance pipki gamma targeting to focal adhesions. We find that y649 phosphorylation does not stimulate directly pipki gamma binding to talin, but may do so indirectly by inhibiting s650 phosphorylation.	SIGNOR-134459
Q96BY2	O95071	0	ubiquitination	down-regulates quantity by destabilization	0.345	We demonstrate that UBR5 interacts physically with MOAP-1, ubiquitylates MOAP-1 in vitro and inhibits MOAP-1 stability in cultured cells.	SIGNOR-278581
Q9Y4R8	P68400	0	phosphorylation	down-regulates	0.2	Here we report that tel2 and tti1 are targeted for degradation within mtorc1 by the scffbxo9 ubiquitin ligase to adjust mtor signalling to growth factor availability. This process is primed by ck2, which translocates to the cytoplasm to mediate mtorc1-specific phosphorylation of tel2/tti1. ere, we show that tel2 is constitutively phosphorylated on conserved serines 487 and 491 by casein kinase 2 (ck2)	SIGNOR-200202
O15409	Q13224	1	transcriptional regulation	up-regulates quantity by expression	0.318	By interacting with CASK, TBR1 regulates several ASD candidate genes, such as GRIN2B, AUTS2 and RELN—all of which are recurrently mutated in ASD. In areas of the brain with overlapping expression patterns, such as in glutamatergic layer 6 neurons, the TBR1–FOXP2 interaction may result in co-ordinated regulation of common downstream targets.	SIGNOR-266834
P60484	P08047	1	dephosphorylation	down-regulates activity	0.421	Moreover, PTEN downregulates p75NTR expression by decreasing DNA-binding activity of Sp1 .\|PTEN dephosphorylates the Sp1 transcription factor , the phosphorylation status of which directly impacts its ability to bind to some DNA promoter regions , .	SIGNOR-277119
Q9Y6M4	P07948	1	phosphorylation	up-regulates quantity by stabilization	0.2	Although there have been more than 40 reports of mass spectrometric studies on phosphorylation at Lyn-S13, the kinase responsible remained unclear. We succeeded in identifying casein kinase 1γ (CK1γ) as the kinase responsible for phosphorylation of Lyn-S13. In HEK293 cells co-expressing Lyn and CK1γ, the phosphorylation level of Lyn-S13 increased significantly. we concluded that S-palmitoylated CK1γ encounters N-myristoylated Lyn and specifically phosphorylates the Ser-13 residue at the Golgi during intracellular protein traffic, as shown schematically in Fig. 8. Phosphorylated dual-lipid-modified Lyn and S-palmitoylated CK1γ are then transported from the Golgi to the plasma membrane.	SIGNOR-275395
Q15300	P40763	1	phosphorylation	up-regulates activity	0.2	In addition, RET/PTC-mediated cellular transformation and proliferation of transformed cells require tyrosine 705 phosphorylation of STAT3 in NIH3T3 cells. We conclude that STAT3 activation by the RET/PTC tyrosine kinase is one of the critical signaling pathways for the regulation of specific genes, such as cyclin D1, vascular endothelial growth factor, and intercellular adhesion molecule 1, and for cellular transformation.	SIGNOR-260917
Q9UBL0	P17612	0	phosphorylation	up-regulates activity	0.2	The specificity of antibody G534 was examined using recombinant full-length rat ARPP-21 phosphorylated by PKA. Radiolabeled ARPP-21 from a reaction containing [γ32P]ATP correlated with the detection of phospho-Ser55-ARPP-21 by immunoblotting (Fig. 1A, left and middle panels).	SIGNOR-263107
P30260	P68400	0	phosphorylation	up-regulates	0.378	We report here that phosphorylation of cdc27, a core subunit of apc, in response to tgf- signaling can facilitate the activation of apc.we have demonstrated that casein kinase ii (ckii) is involved in the phosphorylation of cdc27 in response to tgf- signaling.	SIGNOR-170872
P06493	Q08379	1	phosphorylation	down-regulates	0.674	Cdc2 kinase directly phosphorylates the cis-golgi matrix protein gm130 and is required for golgi fragmentation in mitosis. Mitotic fragmentation of the golgi apparatus can be largely explained by disruption of the interaction between gm130 and the vesicle-docking protein p115. Here we identify a single serine (ser-25) in gm130 as the key phosphorylated target and cdc2 as the responsible kinase	SIGNOR-60281
P04040	Q05655	0	phosphorylation	up-regulates activity	0.266	Endothelin-1 stimulates catalase activity through the PKCδ-mediated phosphorylation of serine 167.	SIGNOR-260904
P06493	Q8IX90	1	phosphorylation	up-regulates activity	0.394	Cdk1 treatment further enhanced the binding of Ska3 2D to Ndc80, suggesting that phosphorylation of other Cdk1 sites in Ska3 further contributes to the Ndc80C-Ska3 interaction, although this contribution is not apparent in our kinetochore localization assay.We next purified the GST-Ndc80C Bonsai construct that lacks the loop region of Ndc80 as well as the coiled coil regions of Ndc80C [17].\|Thus, Ska3 can be phosphorylated by Cdk1 on T358 and T360 sites in vitro.We next tested whether Ska3 was required for Ska1 or Ska2 localization.	SIGNOR-278376
Q96BA8	Q14703	0	cleavage	up-regulates	0.571	Cleavage of oasis by site-1 and site-2 proteases / oasis is cleaved at the membrane under er stress conditions and that its cleaved n-terminal domain translocates into the nucleus;and then activates transcription of target genes	SIGNOR-143785
P46934	O75113	1	monoubiquitination	up-regulates activity	0.448	This observation, together with the monoubiquitination of Nedd4-BP1 by the ubiquitin ligase Nedd4 suggests that the NYN domain proteins of eukaryotes are regulated by monoubiquitination. Given the localization of Nedd4-BP1 to punctuate nuclear bodies, it is likely that they are parts of nuclear RNA-processing complexes that are dependent on monoubiquitination for their assembly.	SIGNOR-272626
Q92538	Q13131	0	phosphorylation	down-regulates	0.2	These results indicate that gbf1 is a novel ampk substrate and that the ampk-mediated phosphorylation of gbf1 at thr(1337) has a critical role, presumably by attenuating the function of gbf1, in the disassembly of the golgi apparatus induced under stress conditions that lower the intracellular atp concentration.	SIGNOR-159639
O60216	Q01196	1	transcriptional regulation	down-regulates quantity by repression	0.283	We observed that depletion of RAD21 (but not CTCF) enhanced RUNX1 transcription in human HL-60 myelocytic leukemia cells	SIGNOR-259973
P16615	Q9UQM7	0	phosphorylation	up-regulates activity	0.397	SERCA2 and SERCA2 mutants S38A, S167A, and S531A were expressed in HEK-293 cells and tested for phosphorylation with CaM kinase. Mutant S38A was not phosphorylated, while mutants S167A and S531A were phosphorylated, suggesting that Ser38 is the site of CaM kinase phosphorylation in SERCA2. This conclusion was supported by the observation that phosphorylation of SERCA2 and mutants S167A and S531A by CaM kinase increased the Vmax for Ca2+ transport, while the Vmax for Ca2+ transport by mutant S38A was unaffected by exposure to a phosphorylation reaction mix.	SIGNOR-250616
P28482	Q9H3M7	1	phosphorylation	down-regulates quantity by destabilization	0.294	ERK-dependent Txnip ubiquitination and proteasome degradation depended upon phosphorylation of a PXTP motif threonine (Thr349) located within the C-terminal α-arrestin domain and proximal to a previously characterized E3 ubiquitin ligase-binding site.	SIGNOR-277468
P49407	P17252	0	phosphorylation	up-regulates activity	0.2	We demonstrate that β-arrestin-1 recruitment to the TCR, and bystander TCR and CXCR4 downregulation, are mechanistically mediated by the TCR-triggered PKC-mediated phosphorylation of β-arrestin-1 at Ser163.	SIGNOR-276619
Q13617	P31941	1	ubiquitination	down-regulates quantity by destabilization	0.251	Human Papillomavirus 16 E7 Stabilizes APOBEC3A Protein by Inhibiting Cullin 2-Dependent Protein Degradation\|Here, we report that the HPV oncoprotein E7 stabilizes the APOBEC3A (A3A) protein in human keratinocytes by inhibiting ubiquitin-dependent protein degradation in a cullin-dependent manner.	SIGNOR-261325
Q96PU5	Q96BR1	0	phosphorylation	down-regulates activity	0.445	Moreover, S422DSGK1, SGK1, and SGK3 also phosphorylated Nedd4-2 and thereby inhibited Nedd4-2 binding to its target.	SIGNOR-280125
P11802	P50613	0	phosphorylation	up-regulates	0.587	Phosphorylation of cdk4 on threonine 172 by a cdk-activating kinase (cak). therefore, formation of the cyclin d-cdk4 complex and phosphorylation of the bound catalytic subunit are independently regulated, and in addition to the requirement for cak activity, serum stimulation is required to promote assembly of the complexes in mammalian cells.	SIGNOR-36549
P06493	Q9BTA9	1	phosphorylation	up-regulates activity	0.2	Cyclin-dependent kinase 1 (Cdk1) phosphorylates WAC, priming its direct interaction with the polo-box domain of Plk1. Knockdown of WAC compromises Plk1 activity and delays mitotic entry.	SIGNOR-265035
P08069	Q9Y4H2	1	phosphorylation	up-regulates	0.802	Our results reveal that igf-1 receptors promote beta-cell development and survival through the irs-2 signalling pathway.	SIGNOR-70477
Q8NFU7	P60484	1	transcriptional regulation	up-regulates quantity by expression	0.373	We also found that TET1 directly binds to the promoter region of PTEN and activates its transcription through demethylation of CpG islands	SIGNOR-259096
P30519	P68400	0	phosphorylation	up-regulates activity	0.335	Carbon monoxide neurotransmission activated by CK2 phosphorylation of heme oxygenase-2. \| CK2 activation is abolished by the S79A mutation but preserved in S179A and T248A mutations, indicating that S79 is the target of CK2-dependent activation of HO2	SIGNOR-250895
Q99952	P04626	1	dephosphorylation	down-regulates quantity by destabilization	0.671	PTPN18 knockdown selectively enhances the EGF-induced tyrosine phosphorylation of the HER2 Y1112, Y1196 and Y1248 sites. \|Whereas the catalytic domain of PTPN18 blocks lysosomal routing and delays the degradation of HER2 by dephosphorylation of HER2 on pY(1112), the PEST domain of PTPN18 promotes K48-linked HER2 ubiquitination and its rapid destruction via the proteasome pathway and an HER2 negative feedback loop.	SIGNOR-262596
Q06413	Q32MK0	0	phosphorylation	up-regulates activity	0.269	Here, we show that phosphorylation of MEF2C on T(80) by skeletal myosin light chain kinase (skMLCK) enhances skeletal and not cardiac myogenesis.\|Here, we show that skMLCK directly phosphorylates MEF2C, leading to p300/PCAF recruitment, increased acetylation of skeletal muscle-specific genes, and enhanced skeletal myogenesis	SIGNOR-264565
Q00535	O95817	1	phosphorylation	down-regulates quantity by destabilization	0.2	CDK5-mediated phosphorylation on S297 promotes BAG3 degradation.	SIGNOR-277502
P45984	P31947	1	phosphorylation	down-regulates	0.2	Jnk phosphorylates 14-3-3zeta_ at ser-184 and 14-3-3sigma_ at ser-189	SIGNOR-124027
Q8TCJ0	Q05655	0	phosphorylation	up-regulates activity	0.271	FBXO25 encodes an orphan F-box protein that determines the substrate specificity of the SCF (SKP1-CUL1-F-box)(FBXO25) ubiquitin ligase complex. An unbiased screen uncovered the prosurvival protein HCLS1-associated protein X-1 (HAX-1) as the bona fide substrate of FBXO25 that is targeted after apoptotic stresses. Protein kinase Cdelta (PRKCD) initiates this process by phosphorylating FBXO25 and HAX-1, thereby spatially directing nuclear FBXO25 to mitochondrial HAX-1.\|Accordingly, PRKCD-induced phosphorylation of Hax-1 at Ser210 and Fbxo25 at Ser178 was associated with decreased expression of Hax-1 in control cells,	SIGNOR-275561
O15519	Q9UNE7	0	ubiquitination	down-regulates quantity by destabilization	0.356	Taken together, our data suggest that CHIP interacts with c-FLIP L in vivo and promotes the ubiquitination of c-FLIP L.\|When we knocked down CHIP, c-FLIP L degradation was inhibited after treatment with 17-AAG, which indicated that CHIP modulated c-FLIP L degradation in the NSCLC cell lines.	SIGNOR-278783
Q01094	P50613	0	phosphorylation	down-regulates	0.493	These results suggest that tfiih-mediated phosphorylation of e2f-1 plays a role in triggering e2f-1 degradation during s phase. here we show that the e2f-1 activation domain interacts with a kinase activity which phosphorylates two sites, ser403 and thr433, within the activation domain.	SIGNOR-69776
Q9Y4K3	P36406	0	ubiquitination	up-regulates activity	0.313	We show here that the upregulation of NF-kappaB by UL144 is dependent upon cellular tripartite motif 23 (TRIM23) protein. We propose a mechanism by which UL144 activates NF-kappaB through a direct interaction with the cellular protein TRIM23 in a complex containing TRAF6. we propose that TRIM23 mediates TRAF6 autoubiquitination in the presence of UL144, resulting in the virally controlled activation of NF-κB stimulation at early times of HCMV infection.	SIGNOR-266655
Q9UQB9	P25963	1	phosphorylation	up-regulates activity	0.2	AURKC directly induces IkappaBalpha activation via an interaction between the two proteins, leading to phosphorylation of IkappaBalpha.\|AURKC phosphorylates IkappaBalpha on S32 and binds its ankyrin repeat domain.	SIGNOR-278470
Q00613	P49137	0	phosphorylation	down-regulates activity	0.519	A potential mechanism for MK2-induced HSF1 inactivation is suggested by the findings that phosphorylation of serine 121 enhances HSF1 binding to HSP90, a major repressor of HSF1.\|Phosphorylation of HSF1 by MAPK activated protein kinase 2 on serine 121, inhibits transcriptional activity and promotes HSP90 binding.	SIGNOR-279541
P27695	P01266	1	transcriptional regulation	up-regulates quantity by expression	0.2	In co-transfection experiments, Ref-1 increases the Pax-8 activating effect on thyroglobulin promoter.	SIGNOR-271694
O95644	Q14164	0	phosphorylation	up-regulates activity	0.2	Phosphorylation of NFATC1 at PIM1 target sites is essential for its ability to promote prostate cancer cell migration and invasion. Here we have identified ten PIM1 target sites in NFATC1 and found that prevention of their phosphorylation significantly decreases the transcriptional activity as well as the pro-migratory and pro-invasive effects of NFATC1 in prostate cancer cells.	SIGNOR-276778
P10997	P16519	0	cleavage	up-regulates activity	0.465	The processing of proinsulin to insulin occurs in the secretory granules at the C-terminal end of pairs of basic amino acids, Arg31-Arg32 and Lys64-Arg65 [9,10]. Following cleavage, by the prohormone convertases, PC3 (also known as PC1) and PC2, the pair of basic amino acids are removed rapidly by carboxypeptidase E (CPE) to produce the mature insulin molecule	SIGNOR-261791
P23246	Q13882	0	phosphorylation	down-regulates activity	0.531	BRK phosphorylates PSF promoting its cytoplasmic localization and cell cycle arrest.\|These data suggest that BRK activity impedes the ability of PSF to bind RNA.To map the PSF tyrosine residues phosphorylated by BRK and assess if the PSF N-terminal is required for phosphorylation, we co-transfected HEK293 cells with various GFP-PSF deletion mutants in the presence or absence myc-BRK-YF.	SIGNOR-279754
Q6ZMI3	Q12955	1	relocalization	up-regulates quantity	0.41	Ankyrin-G is recruited to the nodes of Ranvier by gliomedin, which is produced by Schwann cells and accumulates in the perinodal extracellular matrix. As a ligand for neurofascin-186, gliomedin causes the nodal clustering of this cell adhesion molecule, which in turn recruits to the nodal plasma membrane an ankyrin-G protein network consisting of voltage-gated sodium or potassium channels (KCNQ2/3) and β4-spectrin.	SIGNOR-266725
Q13131	Q9GZT9	1	phosphorylation	down-regulates activity	0.373	Mechanistically, AMPKα1 directly phosphorylated prolyl hydroxylase domain-containing (PHD)2 at serines 61 and 136, which suppressed PHD2-dependent hydroxylation of hypoxia-inducible factor (HIF)1α and subsequent regulation of hepatic hepcidin-related iron signalling.	SIGNOR-277592
Q13315	O15297	0	dephosphorylation	down-regulates	0.488	The negative regulator wip1 plays an important role in inhibiting atm, resulting in a pulse of atm activity.	SIGNOR-185135
P13688	P12931	0	phosphorylation	up-regulates activity	0.426	Recent reports have also suggested that Bgp1 behaves as a signal transduction molecule. Several physiological events promote the Tyr phosphorylation of Bgp1 on one or two Tyr residues within its cytoplasmic domain (Tyr-488 and Tyr-515). BGP becomes Tyr-phosphorylated by Src-like Tyr kinases in activated neutrophils (24) and in human colon carcinoma cellsWe have recently shown that Tyr phosphorylation of the mouse Bgp1 cytoplasmic domain in CT51 mouse colonic carcinoma cells led to its binding to the protein-Tyr phosphatase SHP-1 and that this event required the presence of both Tyr-488 and Tyr-515	SIGNOR-246471
Q14119	Q99967	1	transcriptional regulation	down-regulates quantity by repression	0.2	The transcription factor Vezf1 represses the expression of the antiangiogenic factor Cited2 in endothelial cells	SIGNOR-266883
P29350	Q04759	0	phosphorylation	down-regulates activity	0.2	SHP-1 phosphorylation is mediated through PKC-θ. Here, we show that phosphorylation of SHP-1 in NK cells on the S591 residue by PKC-θ promotes the inhibited SHP-1 'folded' state. Silencing PKC-θ maintains SHP-1 in the active conformation, reduces NK cell activation and cytotoxicity, and promotes tumor progression in vivo.	SIGNOR-277590
P28482	P15336	1	phosphorylation	up-regulates	0.733	Here, we show that in fibroblasts, insulin, epidermal growth factor (egf) and serum activate atf2 via a so far unknown two-step mechanism involving two distinct ras effector pathways: the raf-mek-erk pathway induces phosphorylation of atf2 thr71, whereas subsequent atf2 thr69 phosphorylation requires the ral-ralgds-src-p38 pathway.	SIGNOR-90517
Q14289	Q9ULZ2	1	phosphorylation	up-regulates activity	0.352	In 293 cells expressing recombinant BRDG1 and various PTKs, Tec and Pyk2, but not Btk, Bmx, Lyn, Syk, or c-Abl, induced marked phosphorylation of BRDG1 on tyrosine residues. BRDG1 was also phosphorylated by Tec directly in vitro. Furthermore, BRDG1 was shown to participate in a positive feedback loop by increasing the activity of Tec. BRDG1 thus appears to function as a docking protein acting downstream of Tec in BCR signaling.	SIGNOR-261818
P04637	Q9H0M0	0	ubiquitination	up-regulates activity	0.319	Unlike other E3 ligases, WWP1 increases p53 stability; inhibition of WWP1 expression or expression of a ligase-mutant form results in decreased p53 expression.\|WWP1 associates with p53 and induces p53 ubiquitylation.	SIGNOR-278649
Q9H6S0	P15336	0	transcriptional regulation	up-regulates quantity by expression	0.275	Collectively, these data show that YTHDC2 plays an important role in tumor cells growth and activation/recruitment of c-Jun and ATF-2 to the YTHDC2 promoter is necessary for the transcription of YTHDC2, and that HDAC activity is required for the efficient expression of YTHDC2 in both of hepatocyte and HCC cells.	SIGNOR-269001
Q01196	O60216	0	transcriptional regulation	down-regulates quantity by repression	0.283	We observed that depletion of RAD21 (but not CTCF) enhanced RUNX1 transcription in human HL-60 myelocytic leukemia cells	SIGNOR-259973
P62136	O14965	1	dephosphorylation	down-regulates	0.436	Pp1 is shown to dephosphorylate active stk15 and abolish its activity in vitro.	SIGNOR-110411
P29474	Q05513	0	phosphorylation	down-regulates activity	0.371	The phosphorylation of both S617 and S635 have also been shown to promote increased eNOS-derived NO release (Michell et al., 2002). The phosphorylaiton of S617 can be induced by PKA or Akt activity, and may serve to sensitize eNOS to calmodulin binding and modulate the phosphorylation of other eNOS sites	SIGNOR-251637
P30307	Q99683	1	dephosphorylation	down-regulates activity	0.288	At the interval CDC25C inhibits ASK1, dephosphorylating pThr838 in its activation loop.\|CDC25C dephosphorylates ASK1 to inhibit its activity during the interphase.	SIGNOR-277100
O15304	P42684	0	phosphorylation	up-regulates	0.334	Our results also demonstrate that mutation of the siva-1 tyr48 site abrogates the apoptotic function of siva-1 and that apoptosis induced by siva-1 is dependent on expression of kinase-active arg.	SIGNOR-104992
P17252	Q6ZN44	1	phosphorylation	down-regulates quantity	0.2	We show that protein interacting with C-kinase 1 (PICK1) recruits activated protein kinase Cα (PKCα) to MycUNC5A at the plasma membrane, stimulating its endocytosis. We identify two PKCα phosphorylation sites at serines 408 and 587, as well as dileucine internalization motifs, which are required for this endocytosis.	SIGNOR-268180
Q13950	P56524	0	deacetylation	down-regulates activity	0.524	HDAC4 and HDAC5 deacetylate Runx2, allowing the protein to undergo Smurf-mediated degradation	SIGNOR-227547
P00519	O00213	1	phosphorylation	up-regulates	0.415	The c-abl tyrosine kinase phosphorylates the fe65 adaptor protein to stimulate fe65/amyloid precursor protein nuclear signaling. Here, we show that active c-abl stimulates app/fe65-mediated gene transcription and that this effect is mediated by phosphorylation of fe65 on tyrosine 547 within its second ptb domain.	SIGNOR-123476
Q9Y297	P10070	1	ubiquitination	down-regulates quantity by destabilization	0.651	The phosphorylated gli2 protein interacts with beta-trcp, and is ubiquitinated and degraded by the proteasome	SIGNOR-146109
P07948	P78368	0	phosphorylation	up-regulates quantity by stabilization	0.2	Although there have been more than 40 reports of mass spectrometric studies on phosphorylation at Lyn-S13, the kinase responsible remained unclear. We succeeded in identifying casein kinase 1γ (CK1γ) as the kinase responsible for phosphorylation of Lyn-S13. In HEK293 cells co-expressing Lyn and CK1γ, the phosphorylation level of Lyn-S13 increased significantly. we concluded that S-palmitoylated CK1γ encounters N-myristoylated Lyn and specifically phosphorylates the Ser-13 residue at the Golgi during intracellular protein traffic, as shown schematically in Fig. 8. Phosphorylated dual-lipid-modified Lyn and S-palmitoylated CK1γ are then transported from the Golgi to the plasma membrane.	SIGNOR-275397
P28482	P27708	1	phosphorylation	up-regulates	0.382	Cad is a multifunctional protein that initiates and regulates mammalian de novo pyrimidine biosynthesis. The activation of the pathway required for cell proliferation is a consequence of the phosphorylation of cad thr-456 by mitogen-activated protein (map) kinase.Activated map kinase (erk1/2), the enzyme responsible for the phosphorylation of thr-456, was also present in larger amounts in the nucleus than the cytosol	SIGNOR-137171
Q4G148	P46531	1	glycosylation	up-regulates	0.383	Activity on notch egf repeats was proven by in vitro xylosylation of a mouse notch1 fragment recombinantly produced in sf9 insect cells, a bacterially expressed egf repeat from mouse notch2 modified in vitro by rumi and gxylt2 and in vivo by co-expression of the enzyme with the notch1 fragment.	SIGNOR-177691
P15884	Q9UBE8	0	phosphorylation	down-regulates	0.2	Whereas lef-1 and tcf-4 phosphorylation by nlk (nemo-like kinase) leads to less lef/tcf/beta-catenin complex binding to dna and to lef-1/tcf-4 degradation	SIGNOR-24147
Q16778	Q9HCI7	0	monoubiquitination	down-regulates activity	0.2	MSL1/2 ubiquitylates histone H2B on K 34. Importantly, only mono-ubiquitylation of H2B by MSL1/2 was detected in cells (data not shown), suggesting that MSL1/2, like RNF20/RNF40, was mainly a mono-ubiquitylase under physiological conditions.the MOF-MSL complex functions to promote both H4 K16ac and H2B K34ub. H2B K34ub, in turn, promotes H2B K120ub, H3 K4me3 and K79me2 to facilitate transcription elongation.	SIGNOR-271976
P05106	O15530	0	phosphorylation	down-regulates activity	0.473	PDK1 specifically phosphorylates Thr-753 in 3. Our data argue that phosphorylation of Thr-753, which is conserved in many subunits, reduces the ability of PTB-containing proteins to bind the NXX(pY) motif in 3.	SIGNOR-250266
Q15031	P18848	0	transcriptional regulation	up-regulates quantity by expression	0.251	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-269421
P28482	Q07866	1	phosphorylation	down-regulates	0.271	Phosphorylation of kinesin light chain 1 at serine 460 modulates binding and trafficking of calsyntenin-1mutation of klc1ser460 to an alanine residue, to preclude phosphorylation, increased the binding of calsyntenin-1, whereas mutation to an aspartate residueklc1ser460 is a predicted mitogen-activated protein kinase (mapk) target site, and we show that extracellular-signal-regulated kinase (erk) phosphorylates this residue in vitro.	SIGNOR-172638
P22681	Q9Y2R2	0	dephosphorylation	down-regulates	0.387	The tyrosine phosphatase lyp1 was found to be constitutively associated with the proto-oncogene c-cbl in thymocytes and t cells. Overexpression of lyp1 reduces cbl tyrosine phosphorylation. It is known that cbl is heavily tyrosine phosphorylated after tcr stimulation and can associate with the syk and zap tyrosine kinases, negatively regulating their activities. Tyrosine phosphatases keep cbl in a basally dephosphorylated state.	SIGNOR-65405
Q9HC77	Q9NYY3	0	phosphorylation	up-regulates	0.579	Plk2 phosphorylates the s589 and s595 residues of cpap in vitro and in vivo. This phosphorylation is critical for procentriole formation during the centrosome cycle.	SIGNOR-165999
Q8N752	O94916	1	phosphorylation	up-regulates activity	0.2	However, the siRNA knockdown of CK1α1L significantly reduced the nuclear export of OREBP/TonEBP under hypotonic conditions (Fig. 5F). Taken together, these data suggest that CK1α1L is the kinase that phosphorylates Ser-158 in the regulation of OREBP/TonEBP export.	SIGNOR-274111
Q16777	Q86Y13	0	monoubiquitination	up-regulates activity	0.2	2A-HUB catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatoric component of the repression machinery required for specific gene regulation programs. Thus, 2A-HUB mediates a selective repression of a specific set of chemokine genes in macrophages, critically modulating migratory responses to TLR activation. H2A monoubiquitination acts to prevent FACT recruitment at the transcriptional promoter region, blocking RNA polymerase II release at the early stage of elongation.	SIGNOR-271754
P25098	P32245	1	phosphorylation	down-regulates activity	0.2	Mutagenesis studies revealed that Thr312 and Ser329/330 in the C-terminal tail are potential sites for PKA and GRK phosphorylation and may play an essential role in the recruitment of beta-arrestin to the activated receptor.	SIGNOR-247770
Q16539	Q8TDD2	1	phosphorylation	up-regulates activity	0.408	We therefore propose that Osterix binds to Sp1 sequences on target gene promoters and that its phosphorylation by p38 enhances recruitment of coactivators to form transcriptionally active complexes	SIGNOR-255791
Q96J02	P17275	1	polyubiquitination	down-regulates quantity by destabilization	0.408	Itch promotes Ub conjugation to JunB Molecularly, Itch associated with and induced ubiquitination of JunB, a transcription factor that is involved in TH2 differentiation. However, in Itch−/− T cells under the same conditions, degradation of JunB was markedly delayed.	SIGNOR-272619
Q05513	P46937	1	phosphorylation	down-regulates quantity by destabilization	0.277	Yap and β-catenin are direct substrates of PKCζ.We show here that PKCζ suppresses intestinal stem cell function by promoting the downregulation of β-catenin and Yap through direct phosphorylation.Consistent with MS/MS analysis, mutation to alanine of these two sites completely abolished Yap phosphorylation by PKCζ. Interestingly, S109 and T110 sites were highly conserved among species (Figure S3B), which suggested an important role in Yap regulation.	SIGNOR-276877
Q96AQ6	Q14164	0	phosphorylation	down-regulates quantity by destabilization	0.2	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-276618
P15559	Q16236	0	transcriptional regulation	up-regulates quantity by expression	0.487	In both models, the inducer-modified and Nrf2-bound Keap1 is inactivated and, consequently, newly synthesized Nrf2 proteins bypass Keap1 and translocate into the nucleus, bind to the ARE and drive the expression of Nrf2 target genes such as NAD(P)H quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HMOX1), glutamate-cysteine ligase (GCL) and glutathione S transferases (GSTs).	SIGNOR-256275
O15169	O75581	0	relocalization	down-regulates activity	0.835	The phosphorylation of lrp6 generates a docking site for axin and recruits it to the plasma membrane, where axin is inactivated and/or targeted for degradation by an unknown mechanism.	SIGNOR-148668
O14974	O95835	0	phosphorylation	up-regulates activity	0.47	LATS1 directly and preferentially phosphorylated serine 445 (S445) of MYPT1.\|This suggests that LATS1 promotes MYPT1 to antagonize PLK1 activity.	SIGNOR-278184
P50549	O75582	0	phosphorylation	up-regulates activity	0.463	Activated, overexpressed MSK1 was able to phosphorylate ER81 at Ser191 and Ser216. Mutation of these residues strongly impairs ER81-responsive promoter activity.	SIGNOR-262987
Q99708	P53350	0	phosphorylation	up-regulates activity	0.347	PLK1 targets CtIP to promote microhomology mediated end joining.\|We further showed that the DSB repair factor CtIP is jointly phosphorylated by CDK1 and Aurora A and PLK1.	SIGNOR-279253
P04908	Q86Y13	0	monoubiquitination	up-regulates activity	0.2	2A-HUB catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatoric component of the repression machinery required for specific gene regulation programs. Thus, 2A-HUB mediates a selective repression of a specific set of chemokine genes in macrophages, critically modulating migratory responses to TLR activation. H2A monoubiquitination acts to prevent FACT recruitment at the transcriptional promoter region, blocking RNA polymerase II release at the early stage of elongation.	SIGNOR-271747
P53350	Q96EP1	0	polyubiquitination	down-regulates quantity by destabilization	0.468	Chfr, a mitotic stress checkpoint, plays an important role in cell cycle progression, tumor suppression and the processes that require the E3 ubiquitin ligase activity mediated by the RING finger domain. Chfr stimulates the formation of polyubiquitin chains by ub-conjugating enzymes, and induces the proteasome-dependent degradation of a number of cellular proteins including Plk1 and Aurora A.	SIGNOR-271464
P37840	P68400	0	phosphorylation	up-regulates	0.514	In vitro experiments and two-dimensional phosphopeptide mapping provided further evidence that serine 129 was phosphorylated by ck-1 and ck-2. Moreover, phosphorylation of serine 129 was reduced in vivo upon inhibition of ck-1 or ck-2. These data demonstrate that alpha-synuclein is constitutively phosphorylated within its c terminus and may indicate that the function of alpha-synuclein is regulated by phosphorylation/dephosphorylation.From these data we conclude that _-synuclein is predominantly phosphorylated at serine residue 129. However, a second serine at position 87 is also used for phosphorylation to some extent. together, these data may indicate that ck-1 and ck-2 are involved in the regulation of neuronal function and one may speculate that phosphorylation of _-synuclein could affect its binding to membranes.	SIGNOR-73807
P31629	P30874	1	transcriptional regulation	up-regulates quantity by expression	0.411	Activation of somatostatin receptor II expression by transcription factors MIBP1 and SEF-2 in the murine brain.	SIGNOR-261617

Q16584

P46734

1

phosphorylation

up-regulates activity

0.492

Immunoprecipitated mlk-3 catalyzed the phosphorylation of sek1 in vitro, and co-transfected mlk-3 induced phosphorylation of sek1 and mkk3 at sites required for activation, suggesting direct regulation of these protein kinases.

SIGNOR-45788

O00308

Q9H074

1

ubiquitination

down-regulates quantity by destabilization

0.332

Here, we show that the E6AP carboxyl terminus (HECT)-type ubiquitin ligase WW domain-containing protein 2 (WWP2), a homolog of the HECT-type ubiquitin ligase WWP1, interacts with and targets Paip1 for ubiquitination and proteasomal degradation.

SIGNOR-272842

P63096

P09619

0

phosphorylation

up-regulates activity

0.2

RTKs directly phosphorylate Gαi on Y154, 155, and Y320.

SIGNOR-277232

Q9HC62

Q15418

0

phosphorylation

down-regulates activity

0.2

Here, we determined that d-flow activated the serine/threonine kinase p90RSK, which subsequently phosphorylated threonine 368 (T368) of SENP2. T368 phosphorylation promoted nuclear export of SENP2, leading to downregulation of eNOS expression and upregulation of proinflammatory adhesion molecule expression and apoptosis.

SIGNOR-273839

Q13555

P42261

1

phosphorylation

up-regulates activity

0.63

In this study, CaM-kinase II enhanced kainate currents of expressed glutamate receptor 6 in 293 cells and of wild-type glutamate receptor 1, but not the Ser-627 to Ala mutant, in Xenopus oocytes. | This CaM-kinase II regulatory phosphorylation site is conserved in all AMPA/kainate-type glutamate receptors, and its phosphorylation may be important in enhancing postsynaptic responsiveness as occurs during synaptic plasticity.

SIGNOR-250697

P12931

P61978

1

phosphorylation

down-regulates

0.603

We show that hnrnp k and the c-src kinase specifically interact with each other, leading to c-src activation and tyrosine phosphorylation of hnrnp k in vivo and in vitro. c-src-mediated phosphorylation reversibly inhibits the binding of hnrnp k to the differentiation control element (dice) of the lox mrna 3' untranslated region in vitro and specifically derepresses the translation of dice-bearing mrnas in vivo.We confirmed that tyr 230, 234, 236, and 380 are phosphorylated and identified two additional targets of c-src, tyr 72 and tyr 225 (data not shown).

SIGNOR-88911

Q03112

P24941

0

phosphorylation

up-regulates activity

0.296

The motif harbouring S436 is a target of CDK2 and CDK3 kinases, which interacted with EVI1-WT. The methyltransferase DNMT3A bound preferentially to EVI1-WT compared with EVI1-S436A, and a hypomethylated cell population associated by EVI1-WT expression in murine haematopoietic progenitors is not maintained with EVI1-S436A.

SIGNOR-273426

P48729

P55957

1

phosphorylation

up-regulates activity

0.286

Here we report that Bid is phosphorylated by casein kinase I (CKI) and casein kinase II (CKII). Inhibition of CKI and CKII accelerated Fas-mediated apoptosis and Bid cleavage, whereas hyperactivity of the kinases delayed apoptosis. | These results suggest that residues S61, S64, and to a much lesser extent T58 are sites of phosphorylation of Bid.

SIGNOR-250785

Q05397

P09769

0

phosphorylation

up-regulates

0.552

Phosphorylated on tyrosine residues upon activation. Phosphorylation at tyr-925 is important for interaction with grb2 and depends on the complex formation between fak and the src-kinase fgr.

SIGNOR-94405

Q8N257

Q14493

0

translation regulation

up-regulates quantity by expression

0.2

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

SIGNOR-265388

P24941

P78317

1

phosphorylation

up-regulates activity

0.2

Here we reported that CDK2 could phosphorylate RNF4 on T26 and T112 and enhance RNF4 E3 ligase activity, which is important for MDC1 degradation and proper HR repair during S phase.

SIGNOR-276900

P17655

Q15078

1

cleavage

up-regulates activity

0.565

Calpains also modulate the activity of CDK5. Physiologically, CDK 5 is activated by p35 and its cleaved product p25. The latter has a longer half life than p35 and therefore it is a more potent activator of CDK5. The cleavage of p35 to p25 is mediated by calpain

SIGNOR-251610

Q9H3Y6

P45985

1

phosphorylation

down-regulates activity

0.2

SRMS directly phosphorylates MKK4 and inhibits MKK4-JNK-c-Jun activation upon platinum treatment. Platinum treatment-induced ROS activates SRMS, which inhibits MKK4 kinase activity by directly phosphorylating MKK4 at Y269 and Y307, and consequently attenuates MKK4-JNK activation.

SIGNOR-277902

P06493

P18031

1

phosphorylation

up-regulates activity

0.502

Cdk1-cyclin B1 directly phosphorylates PTP1B at serine 386 in a kinase assay. Recombinant Plk1 phosphorylates PTP1B on serine 286 and 393 in vitro, however, it requires a priming phosphorylation by Cdk1 at serine 386 highlighting a novel co-operation between Cdk1 and Plk1 in the regulation of PTP1B.|Finally, phosphorylation on serine 286 enhanced PTP1B phosphatase activity.

SIGNOR-272970

Q15831

P17612

0

phosphorylation

up-regulates activity

0.502

Phosphorylation of the protein kinase mutated in Peutz-Jeghers cancer syndrome, LKB1/STK11, at Ser431 by p90(RSK) and cAMP-dependent protein kinase, but not its farnesylation at Cys(433), is essential for LKB1 to suppress cell growth.

SIGNOR-250055

O60331

P12931

0

phosphorylation

up-regulates

0.285

Phosphorylation by src of the tyrosine adjacent to s650 (y649 in human pipki gamma) was shown to enhance pipki gamma targeting to focal adhesions. We find that y649 phosphorylation does not stimulate directly pipki gamma binding to talin, but may do so indirectly by inhibiting s650 phosphorylation.

SIGNOR-134459

Q96BY2

O95071

0

ubiquitination

down-regulates quantity by destabilization

0.345

We demonstrate that UBR5 interacts physically with MOAP-1, ubiquitylates MOAP-1 in vitro and inhibits MOAP-1 stability in cultured cells.

SIGNOR-278581

Q9Y4R8

P68400

0

phosphorylation

down-regulates

0.2

Here we report that tel2 and tti1 are targeted for degradation within mtorc1 by the scffbxo9 ubiquitin ligase to adjust mtor signalling to growth factor availability. This process is primed by ck2, which translocates to the cytoplasm to mediate mtorc1-specific phosphorylation of tel2/tti1. ere, we show that tel2 is constitutively phosphorylated on conserved serines 487 and 491 by casein kinase 2 (ck2)

SIGNOR-200202

O15409

Q13224

1

transcriptional regulation

up-regulates quantity by expression

0.318

By interacting with CASK, TBR1 regulates several ASD candidate genes, such as GRIN2B, AUTS2 and RELN—all of which are recurrently mutated in ASD. In areas of the brain with overlapping expression patterns, such as in glutamatergic layer 6 neurons, the TBR1–FOXP2 interaction may result in co-ordinated regulation of common downstream targets.

SIGNOR-266834

P60484

P08047

1

dephosphorylation

down-regulates activity

0.421

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

SIGNOR-277119

Q9Y6M4

P07948

1

phosphorylation

up-regulates quantity by stabilization

0.2

Although there have been more than 40 reports of mass spectrometric studies on phosphorylation at Lyn-S13, the kinase responsible remained unclear. We succeeded in identifying casein kinase 1γ (CK1γ) as the kinase responsible for phosphorylation of Lyn-S13. In HEK293 cells co-expressing Lyn and CK1γ, the phosphorylation level of Lyn-S13 increased significantly. we concluded that S-palmitoylated CK1γ encounters N-myristoylated Lyn and specifically phosphorylates the Ser-13 residue at the Golgi during intracellular protein traffic, as shown schematically in Fig. 8. Phosphorylated dual-lipid-modified Lyn and S-palmitoylated CK1γ are then transported from the Golgi to the plasma membrane.

SIGNOR-275395

Q15300

P40763

1

phosphorylation

up-regulates activity

0.2

In addition, RET/PTC-mediated cellular transformation and proliferation of transformed cells require tyrosine 705 phosphorylation of STAT3 in NIH3T3 cells. We conclude that STAT3 activation by the RET/PTC tyrosine kinase is one of the critical signaling pathways for the regulation of specific genes, such as cyclin D1, vascular endothelial growth factor, and intercellular adhesion molecule 1, and for cellular transformation.

SIGNOR-260917

Q9UBL0

P17612

0

phosphorylation

up-regulates activity

0.2

The specificity of antibody G534 was examined using recombinant full-length rat ARPP-21 phosphorylated by PKA. Radiolabeled ARPP-21 from a reaction containing [γ32P]ATP correlated with the detection of phospho-Ser55-ARPP-21 by immunoblotting (Fig. 1A, left and middle panels).

SIGNOR-263107

P30260

P68400

0

phosphorylation

up-regulates

0.378

We report here that phosphorylation of cdc27, a core subunit of apc, in response to tgf- signaling can facilitate the activation of apc.we have demonstrated that casein kinase ii (ckii) is involved in the phosphorylation of cdc27 in response to tgf- signaling.

SIGNOR-170872

P06493

Q08379

1

phosphorylation

down-regulates

0.674

Cdc2 kinase directly phosphorylates the cis-golgi matrix protein gm130 and is required for golgi fragmentation in mitosis. Mitotic fragmentation of the golgi apparatus can be largely explained by disruption of the interaction between gm130 and the vesicle-docking protein p115. Here we identify a single serine (ser-25) in gm130 as the key phosphorylated target and cdc2 as the responsible kinase

SIGNOR-60281

P04040

Q05655

0

phosphorylation

up-regulates activity

0.266

Endothelin-1 stimulates catalase activity through the PKCδ-mediated phosphorylation of serine 167.

SIGNOR-260904

P06493

Q8IX90

1

phosphorylation

up-regulates activity

0.394

Cdk1 treatment further enhanced the binding of Ska3 2D to Ndc80, suggesting that phosphorylation of other Cdk1 sites in Ska3 further contributes to the Ndc80C-Ska3 interaction, although this contribution is not apparent in our kinetochore localization assay.We next purified the GST-Ndc80C Bonsai construct that lacks the loop region of Ndc80 as well as the coiled coil regions of Ndc80C [17].|Thus, Ska3 can be phosphorylated by Cdk1 on T358 and T360 sites in vitro.We next tested whether Ska3 was required for Ska1 or Ska2 localization.

SIGNOR-278376

Q96BA8

Q14703

0

cleavage

up-regulates

0.571

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

SIGNOR-143785

P46934

O75113

1

monoubiquitination

up-regulates activity

0.448

This observation, together with the monoubiquitination of Nedd4-BP1 by the ubiquitin ligase Nedd4 suggests that the NYN domain proteins of eukaryotes are regulated by monoubiquitination. Given the localization of Nedd4-BP1 to punctuate nuclear bodies, it is likely that they are parts of nuclear RNA-processing complexes that are dependent on monoubiquitination for their assembly.

SIGNOR-272626

Q92538

Q13131

0

phosphorylation

down-regulates

0.2

These results indicate that gbf1 is a novel ampk substrate and that the ampk-mediated phosphorylation of gbf1 at thr(1337) has a critical role, presumably by attenuating the function of gbf1, in the disassembly of the golgi apparatus induced under stress conditions that lower the intracellular atp concentration.

SIGNOR-159639

O60216

Q01196

1

transcriptional regulation

down-regulates quantity by repression

0.283

We observed that depletion of RAD21 (but not CTCF) enhanced RUNX1 transcription in human HL-60 myelocytic leukemia cells

SIGNOR-259973

P16615

Q9UQM7

0

phosphorylation

up-regulates activity

0.397

SERCA2 and SERCA2 mutants S38A, S167A, and S531A were expressed in HEK-293 cells and tested for phosphorylation with CaM kinase. Mutant S38A was not phosphorylated, while mutants S167A and S531A were phosphorylated, suggesting that Ser38 is the site of CaM kinase phosphorylation in SERCA2. This conclusion was supported by the observation that phosphorylation of SERCA2 and mutants S167A and S531A by CaM kinase increased the Vmax for Ca2+ transport, while the Vmax for Ca2+ transport by mutant S38A was unaffected by exposure to a phosphorylation reaction mix.

SIGNOR-250616

P28482

Q9H3M7

1

phosphorylation

down-regulates quantity by destabilization

0.294

ERK-dependent Txnip ubiquitination and proteasome degradation depended upon phosphorylation of a PXTP motif threonine (Thr349) located within the C-terminal α-arrestin domain and proximal to a previously characterized E3 ubiquitin ligase-binding site.

SIGNOR-277468

P49407

P17252

0

phosphorylation

up-regulates activity

0.2

We demonstrate that β-arrestin-1 recruitment to the TCR, and bystander TCR and CXCR4 downregulation, are mechanistically mediated by the TCR-triggered PKC-mediated phosphorylation of β-arrestin-1 at Ser163.

SIGNOR-276619

Q13617

P31941

1

ubiquitination

down-regulates quantity by destabilization

0.251

Human Papillomavirus 16 E7 Stabilizes APOBEC3A Protein by Inhibiting Cullin 2-Dependent Protein Degradation|Here, we report that the HPV oncoprotein E7 stabilizes the APOBEC3A (A3A) protein in human keratinocytes by inhibiting ubiquitin-dependent protein degradation in a cullin-dependent manner.

SIGNOR-261325

Q96PU5

Q96BR1

0

phosphorylation

down-regulates activity

0.445

Moreover, S422DSGK1, SGK1, and SGK3 also phosphorylated Nedd4-2 and thereby inhibited Nedd4-2 binding to its target.

SIGNOR-280125

P11802

P50613

0

phosphorylation

up-regulates

0.587

Phosphorylation of cdk4 on threonine 172 by a cdk-activating kinase (cak). therefore, formation of the cyclin d-cdk4 complex and phosphorylation of the bound catalytic subunit are independently regulated, and in addition to the requirement for cak activity, serum stimulation is required to promote assembly of the complexes in mammalian cells.

SIGNOR-36549

P06493

Q9BTA9

1

phosphorylation

up-regulates activity

0.2

Cyclin-dependent kinase 1 (Cdk1) phosphorylates WAC, priming its direct interaction with the polo-box domain of Plk1. Knockdown of WAC compromises Plk1 activity and delays mitotic entry.

SIGNOR-265035

P08069

Q9Y4H2

1

phosphorylation

up-regulates

0.802

Our results reveal that igf-1 receptors promote beta-cell development and survival through the irs-2 signalling pathway.

SIGNOR-70477

Q8NFU7

P60484

1

transcriptional regulation

up-regulates quantity by expression

0.373

We also found that TET1 directly binds to the promoter region of PTEN and activates its transcription through demethylation of CpG islands

SIGNOR-259096

P30519

P68400

0

phosphorylation

up-regulates activity

0.335

Carbon monoxide neurotransmission activated by CK2 phosphorylation of heme oxygenase-2. | CK2 activation is abolished by the S79A mutation but preserved in S179A and T248A mutations, indicating that S79 is the target of CK2-dependent activation of HO2

SIGNOR-250895

Q99952

P04626

1

dephosphorylation

down-regulates quantity by destabilization

0.671

PTPN18 knockdown selectively enhances the EGF-induced tyrosine phosphorylation of the HER2 Y1112, Y1196 and Y1248 sites. |Whereas the catalytic domain of PTPN18 blocks lysosomal routing and delays the degradation of HER2 by dephosphorylation of HER2 on pY(1112), the PEST domain of PTPN18 promotes K48-linked HER2 ubiquitination and its rapid destruction via the proteasome pathway and an HER2 negative feedback loop.

SIGNOR-262596

Q06413

Q32MK0

0

phosphorylation

up-regulates activity

0.269

Here, we show that phosphorylation of MEF2C on T(80) by skeletal myosin light chain kinase (skMLCK) enhances skeletal and not cardiac myogenesis.|Here, we show that skMLCK directly phosphorylates MEF2C, leading to p300/PCAF recruitment, increased acetylation of skeletal muscle-specific genes, and enhanced skeletal myogenesis

SIGNOR-264565

Q00535

O95817

1

phosphorylation

down-regulates quantity by destabilization

0.2

CDK5-mediated phosphorylation on S297 promotes BAG3 degradation.

SIGNOR-277502

P45984

P31947

1

phosphorylation

down-regulates

0.2

Jnk phosphorylates 14-3-3zeta_ at ser-184 and 14-3-3sigma_ at ser-189

SIGNOR-124027

Q8TCJ0

Q05655

0

phosphorylation

up-regulates activity

0.271

FBXO25 encodes an orphan F-box protein that determines the substrate specificity of the SCF (SKP1-CUL1-F-box)(FBXO25) ubiquitin ligase complex. An unbiased screen uncovered the prosurvival protein HCLS1-associated protein X-1 (HAX-1) as the bona fide substrate of FBXO25 that is targeted after apoptotic stresses. Protein kinase Cdelta (PRKCD) initiates this process by phosphorylating FBXO25 and HAX-1, thereby spatially directing nuclear FBXO25 to mitochondrial HAX-1.|Accordingly, PRKCD-induced phosphorylation of Hax-1 at Ser210 and Fbxo25 at Ser178 was associated with decreased expression of Hax-1 in control cells,

SIGNOR-275561

O15519

Q9UNE7

0

ubiquitination

down-regulates quantity by destabilization

0.356

Taken together, our data suggest that CHIP interacts with c-FLIP L in vivo and promotes the ubiquitination of c-FLIP L.|When we knocked down CHIP, c-FLIP L degradation was inhibited after treatment with 17-AAG, which indicated that CHIP modulated c-FLIP L degradation in the NSCLC cell lines.

SIGNOR-278783

Q01094

P50613

0

phosphorylation

down-regulates

0.493

These results suggest that tfiih-mediated phosphorylation of e2f-1 plays a role in triggering e2f-1 degradation during s phase. here we show that the e2f-1 activation domain interacts with a kinase activity which phosphorylates two sites, ser403 and thr433, within the activation domain.

SIGNOR-69776

Q9Y4K3

P36406

0

ubiquitination

up-regulates activity

0.313

We show here that the upregulation of NF-kappaB by UL144 is dependent upon cellular tripartite motif 23 (TRIM23) protein. We propose a mechanism by which UL144 activates NF-kappaB through a direct interaction with the cellular protein TRIM23 in a complex containing TRAF6. we propose that TRIM23 mediates TRAF6 autoubiquitination in the presence of UL144, resulting in the virally controlled activation of NF-κB stimulation at early times of HCMV infection.

SIGNOR-266655

Q9UQB9

P25963

1

phosphorylation

up-regulates activity

0.2

AURKC directly induces IkappaBalpha activation via an interaction between the two proteins, leading to phosphorylation of IkappaBalpha.|AURKC phosphorylates IkappaBalpha on S32 and binds its ankyrin repeat domain.

SIGNOR-278470

Q00613

P49137

0

phosphorylation

down-regulates activity

0.519

A potential mechanism for MK2-induced HSF1 inactivation is suggested by the findings that phosphorylation of serine 121 enhances HSF1 binding to HSP90, a major repressor of HSF1.|Phosphorylation of HSF1 by MAPK activated protein kinase 2 on serine 121, inhibits transcriptional activity and promotes HSP90 binding.

SIGNOR-279541

P27695

P01266

1

transcriptional regulation

up-regulates quantity by expression

0.2

In co-transfection experiments, Ref-1 increases the Pax-8 activating effect on thyroglobulin promoter.

SIGNOR-271694

O95644

Q14164

0

phosphorylation

up-regulates activity

0.2

Phosphorylation of NFATC1 at PIM1 target sites is essential for its ability to promote prostate cancer cell migration and invasion. Here we have identified ten PIM1 target sites in NFATC1 and found that prevention of their phosphorylation significantly decreases the transcriptional activity as well as the pro-migratory and pro-invasive effects of NFATC1 in prostate cancer cells.

SIGNOR-276778

P10997

P16519

0

cleavage

up-regulates activity

0.465

The processing of proinsulin to insulin occurs in the secretory granules at the C-terminal end of pairs of basic amino acids, Arg31-Arg32 and Lys64-Arg65 [9,10]. Following cleavage, by the prohormone convertases, PC3 (also known as PC1) and PC2, the pair of basic amino acids are removed rapidly by carboxypeptidase E (CPE) to produce the mature insulin molecule

SIGNOR-261791

P23246

Q13882

0

phosphorylation

down-regulates activity

0.531

BRK phosphorylates PSF promoting its cytoplasmic localization and cell cycle arrest.|These data suggest that BRK activity impedes the ability of PSF to bind RNA.To map the PSF tyrosine residues phosphorylated by BRK and assess if the PSF N-terminal is required for phosphorylation, we co-transfected HEK293 cells with various GFP-PSF deletion mutants in the presence or absence myc-BRK-YF.

SIGNOR-279754

Q6ZMI3

Q12955

1

relocalization

up-regulates quantity

0.41

Ankyrin-G is recruited to the nodes of Ranvier by gliomedin, which is produced by Schwann cells and accumulates in the perinodal extracellular matrix. As a ligand for neurofascin-186, gliomedin causes the nodal clustering of this cell adhesion molecule, which in turn recruits to the nodal plasma membrane an ankyrin-G protein network consisting of voltage-gated sodium or potassium channels (KCNQ2/3) and β4-spectrin.

SIGNOR-266725

Q13131

Q9GZT9

1

phosphorylation

down-regulates activity

0.373

Mechanistically, AMPKα1 directly phosphorylated prolyl hydroxylase domain-containing (PHD)2 at serines 61 and 136, which suppressed PHD2-dependent hydroxylation of hypoxia-inducible factor (HIF)1α and subsequent regulation of hepatic hepcidin-related iron signalling.

SIGNOR-277592

Q13315

O15297

0

dephosphorylation

down-regulates

0.488

The negative regulator wip1 plays an important role in inhibiting atm, resulting in a pulse of atm activity.

SIGNOR-185135

P13688

P12931

0

phosphorylation

up-regulates activity

0.426

Recent reports have also suggested that Bgp1 behaves as a signal transduction molecule. Several physiological events promote the Tyr phosphorylation of Bgp1 on one or two Tyr residues within its cytoplasmic domain (Tyr-488 and Tyr-515). BGP becomes Tyr-phosphorylated by Src-like Tyr kinases in activated neutrophils (24) and in human colon carcinoma cellsWe have recently shown that Tyr phosphorylation of the mouse Bgp1 cytoplasmic domain in CT51 mouse colonic carcinoma cells led to its binding to the protein-Tyr phosphatase SHP-1 and that this event required the presence of both Tyr-488 and Tyr-515

SIGNOR-246471

Q14119

Q99967

1

transcriptional regulation

down-regulates quantity by repression

0.2

The transcription factor Vezf1 represses the expression of the antiangiogenic factor Cited2 in endothelial cells

SIGNOR-266883

P29350

Q04759

0

phosphorylation

down-regulates activity

0.2

SHP-1 phosphorylation is mediated through PKC-θ. Here, we show that phosphorylation of SHP-1 in NK cells on the S591 residue by PKC-θ promotes the inhibited SHP-1 'folded' state. Silencing PKC-θ maintains SHP-1 in the active conformation, reduces NK cell activation and cytotoxicity, and promotes tumor progression in vivo.

SIGNOR-277590

P28482

P15336

1

phosphorylation

up-regulates

0.733

Here, we show that in fibroblasts, insulin, epidermal growth factor (egf) and serum activate atf2 via a so far unknown two-step mechanism involving two distinct ras effector pathways: the raf-mek-erk pathway induces phosphorylation of atf2 thr71, whereas subsequent atf2 thr69 phosphorylation requires the ral-ralgds-src-p38 pathway.

SIGNOR-90517

Q14289

Q9ULZ2

1

phosphorylation

up-regulates activity

0.352

In 293 cells expressing recombinant BRDG1 and various PTKs, Tec and Pyk2, but not Btk, Bmx, Lyn, Syk, or c-Abl, induced marked phosphorylation of BRDG1 on tyrosine residues. BRDG1 was also phosphorylated by Tec directly in vitro. Furthermore, BRDG1 was shown to participate in a positive feedback loop by increasing the activity of Tec. BRDG1 thus appears to function as a docking protein acting downstream of Tec in BCR signaling.

SIGNOR-261818

P04637

Q9H0M0

0

ubiquitination

up-regulates activity

0.319

Unlike other E3 ligases, WWP1 increases p53 stability; inhibition of WWP1 expression or expression of a ligase-mutant form results in decreased p53 expression.|WWP1 associates with p53 and induces p53 ubiquitylation.

SIGNOR-278649

Q9H6S0

P15336

0

transcriptional regulation

up-regulates quantity by expression

0.275

Collectively, these data show that YTHDC2 plays an important role in tumor cells growth and activation/recruitment of c-Jun and ATF-2 to the YTHDC2 promoter is necessary for the transcription of YTHDC2, and that HDAC activity is required for the efficient expression of YTHDC2 in both of hepatocyte and HCC cells.

SIGNOR-269001

Q01196

O60216

0

transcriptional regulation

down-regulates quantity by repression

0.283

We observed that depletion of RAD21 (but not CTCF) enhanced RUNX1 transcription in human HL-60 myelocytic leukemia cells

SIGNOR-259973

P62136

O14965

1

dephosphorylation

down-regulates

0.436

Pp1 is shown to dephosphorylate active stk15 and abolish its activity in vitro.

SIGNOR-110411

P29474

Q05513

0

phosphorylation

down-regulates activity

0.371

The phosphorylation of both S617 and S635 have also been shown to promote increased eNOS-derived NO release (Michell et al., 2002). The phosphorylaiton of S617 can be induced by PKA or Akt activity, and may serve to sensitize eNOS to calmodulin binding and modulate the phosphorylation of other eNOS sites

SIGNOR-251637

P30307

Q99683

1

dephosphorylation

down-regulates activity

0.288

At the interval CDC25C inhibits ASK1, dephosphorylating pThr838 in its activation loop.|CDC25C dephosphorylates ASK1 to inhibit its activity during the interphase.

SIGNOR-277100

O15304

P42684

0

phosphorylation

up-regulates

0.334

Our results also demonstrate that mutation of the siva-1 tyr48 site abrogates the apoptotic function of siva-1 and that apoptosis induced by siva-1 is dependent on expression of kinase-active arg.

SIGNOR-104992

P17252

Q6ZN44

1

phosphorylation

down-regulates quantity

0.2

We show that protein interacting with C-kinase 1 (PICK1) recruits activated protein kinase Cα (PKCα) to MycUNC5A at the plasma membrane, stimulating its endocytosis. We identify two PKCα phosphorylation sites at serines 408 and 587, as well as dileucine internalization motifs, which are required for this endocytosis.

SIGNOR-268180

Q13950

P56524

0

deacetylation

down-regulates activity

0.524

HDAC4 and HDAC5 deacetylate Runx2, allowing the protein to undergo Smurf-mediated degradation

SIGNOR-227547

P00519

O00213

1

phosphorylation

up-regulates

0.415

The c-abl tyrosine kinase phosphorylates the fe65 adaptor protein to stimulate fe65/amyloid precursor protein nuclear signaling. Here, we show that active c-abl stimulates app/fe65-mediated gene transcription and that this effect is mediated by phosphorylation of fe65 on tyrosine 547 within its second ptb domain.

SIGNOR-123476

Q9Y297

P10070

1

ubiquitination

down-regulates quantity by destabilization

0.651

The phosphorylated gli2 protein interacts with beta-trcp, and is ubiquitinated and degraded by the proteasome

SIGNOR-146109

P07948

P78368

0

phosphorylation

up-regulates quantity by stabilization

0.2

Although there have been more than 40 reports of mass spectrometric studies on phosphorylation at Lyn-S13, the kinase responsible remained unclear. We succeeded in identifying casein kinase 1γ (CK1γ) as the kinase responsible for phosphorylation of Lyn-S13. In HEK293 cells co-expressing Lyn and CK1γ, the phosphorylation level of Lyn-S13 increased significantly. we concluded that S-palmitoylated CK1γ encounters N-myristoylated Lyn and specifically phosphorylates the Ser-13 residue at the Golgi during intracellular protein traffic, as shown schematically in Fig. 8. Phosphorylated dual-lipid-modified Lyn and S-palmitoylated CK1γ are then transported from the Golgi to the plasma membrane.

SIGNOR-275397

P28482

P27708

1

phosphorylation

up-regulates

0.382

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

SIGNOR-137171

Q4G148

P46531

1

glycosylation

up-regulates

0.383

Activity on notch egf repeats was proven by in vitro xylosylation of a mouse notch1 fragment recombinantly produced in sf9 insect cells, a bacterially expressed egf repeat from mouse notch2 modified in vitro by rumi and gxylt2 and in vivo by co-expression of the enzyme with the notch1 fragment.

SIGNOR-177691

P15884

Q9UBE8

0

phosphorylation

down-regulates

0.2

Whereas lef-1 and tcf-4 phosphorylation by nlk (nemo-like kinase) leads to less lef/tcf/beta-catenin complex binding to dna and to lef-1/tcf-4 degradation

SIGNOR-24147

Q16778

Q9HCI7

0

monoubiquitination

down-regulates activity

0.2

MSL1/2 ubiquitylates histone H2B on K 34. Importantly, only mono-ubiquitylation of H2B by MSL1/2 was detected in cells (data not shown), suggesting that MSL1/2, like RNF20/RNF40, was mainly a mono-ubiquitylase under physiological conditions.the MOF-MSL complex functions to promote both H4 K16ac and H2B K34ub. H2B K34ub, in turn, promotes H2B K120ub, H3 K4me3 and K79me2 to facilitate transcription elongation.

SIGNOR-271976

P05106

O15530

0

phosphorylation

down-regulates activity

0.473

PDK1 specifically phosphorylates Thr-753 in 3. Our data argue that phosphorylation of Thr-753, which is conserved in many subunits, reduces the ability of PTB-containing proteins to bind the NXX(pY) motif in 3.

SIGNOR-250266

Q15031

P18848

0

transcriptional regulation

up-regulates quantity by expression

0.251

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-269421

P28482

Q07866

1

phosphorylation

down-regulates

0.271

Phosphorylation of kinesin light chain 1 at serine 460 modulates binding and trafficking of calsyntenin-1mutation of klc1ser460 to an alanine residue, to preclude phosphorylation, increased the binding of calsyntenin-1, whereas mutation to an aspartate residueklc1ser460 is a predicted mitogen-activated protein kinase (mapk) target site, and we show that extracellular-signal-regulated kinase (erk) phosphorylates this residue in vitro.

SIGNOR-172638

P22681

Q9Y2R2

0

dephosphorylation

down-regulates

0.387

The tyrosine phosphatase lyp1 was found to be constitutively associated with the proto-oncogene c-cbl in thymocytes and t cells. Overexpression of lyp1 reduces cbl tyrosine phosphorylation. It is known that cbl is heavily tyrosine phosphorylated after tcr stimulation and can associate with the syk and zap tyrosine kinases, negatively regulating their activities. Tyrosine phosphatases keep cbl in a basally dephosphorylated state.

SIGNOR-65405

Q9HC77

Q9NYY3

0

phosphorylation

up-regulates

0.579

Plk2 phosphorylates the s589 and s595 residues of cpap in vitro and in vivo. This phosphorylation is critical for procentriole formation during the centrosome cycle.

SIGNOR-165999

Q8N752

O94916

1

phosphorylation

up-regulates activity

0.2

However, the siRNA knockdown of CK1α1L significantly reduced the nuclear export of OREBP/TonEBP under hypotonic conditions (Fig. 5F). Taken together, these data suggest that CK1α1L is the kinase that phosphorylates Ser-158 in the regulation of OREBP/TonEBP export.

SIGNOR-274111

Q16777

Q86Y13

0

monoubiquitination

up-regulates activity

0.2

2A-HUB catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatoric component of the repression machinery required for specific gene regulation programs. Thus, 2A-HUB mediates a selective repression of a specific set of chemokine genes in macrophages, critically modulating migratory responses to TLR activation. H2A monoubiquitination acts to prevent FACT recruitment at the transcriptional promoter region, blocking RNA polymerase II release at the early stage of elongation.

SIGNOR-271754

P25098

P32245

1

phosphorylation

down-regulates activity

0.2

Mutagenesis studies revealed that Thr312 and Ser329/330 in the C-terminal tail are potential sites for PKA and GRK phosphorylation and may play an essential role in the recruitment of beta-arrestin to the activated receptor.

SIGNOR-247770

Q16539

Q8TDD2

1

phosphorylation

up-regulates activity

0.408

We therefore propose that Osterix binds to Sp1 sequences on target gene promoters and that its phosphorylation by p38 enhances recruitment of coactivators to form transcriptionally active complexes

SIGNOR-255791

Q96J02

P17275

1

polyubiquitination

down-regulates quantity by destabilization

0.408

Itch promotes Ub conjugation to JunB Molecularly, Itch associated with and induced ubiquitination of JunB, a transcription factor that is involved in TH2 differentiation. However, in Itch−/− T cells under the same conditions, degradation of JunB was markedly delayed.

SIGNOR-272619

Q05513

P46937

1

phosphorylation

down-regulates quantity by destabilization

0.277

Yap and β-catenin are direct substrates of PKCζ.We show here that PKCζ suppresses intestinal stem cell function by promoting the downregulation of β-catenin and Yap through direct phosphorylation.Consistent with MS/MS analysis, mutation to alanine of these two sites completely abolished Yap phosphorylation by PKCζ. Interestingly, S109 and T110 sites were highly conserved among species (Figure S3B), which suggested an important role in Yap regulation.

SIGNOR-276877

Q96AQ6

Q14164

0

phosphorylation

down-regulates quantity by destabilization

0.2

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-276618

P15559

Q16236

0

transcriptional regulation

up-regulates quantity by expression

0.487

In both models, the inducer-modified and Nrf2-bound Keap1 is inactivated and, consequently, newly synthesized Nrf2 proteins bypass Keap1 and translocate into the nucleus, bind to the ARE and drive the expression of Nrf2 target genes such as NAD(P)H quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HMOX1), glutamate-cysteine ligase (GCL) and glutathione S transferases (GSTs).

SIGNOR-256275

O15169

O75581

0

relocalization

down-regulates activity

0.835

The phosphorylation of lrp6 generates a docking site for axin and recruits it to the plasma membrane, where axin is inactivated and/or targeted for degradation by an unknown mechanism.

SIGNOR-148668

O14974

O95835

0

phosphorylation

up-regulates activity

0.47

LATS1 directly and preferentially phosphorylated serine 445 (S445) of MYPT1.|This suggests that LATS1 promotes MYPT1 to antagonize PLK1 activity.

SIGNOR-278184

P50549

O75582

0

phosphorylation

up-regulates activity

0.463

Activated, overexpressed MSK1 was able to phosphorylate ER81 at Ser191 and Ser216. Mutation of these residues strongly impairs ER81-responsive promoter activity.

SIGNOR-262987

Q99708

P53350

0

phosphorylation

up-regulates activity

0.347

PLK1 targets CtIP to promote microhomology mediated end joining.|We further showed that the DSB repair factor CtIP is jointly phosphorylated by CDK1 and Aurora A and PLK1.

SIGNOR-279253

P04908

Q86Y13

0

monoubiquitination

up-regulates activity

0.2

2A-HUB catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatoric component of the repression machinery required for specific gene regulation programs. Thus, 2A-HUB mediates a selective repression of a specific set of chemokine genes in macrophages, critically modulating migratory responses to TLR activation. H2A monoubiquitination acts to prevent FACT recruitment at the transcriptional promoter region, blocking RNA polymerase II release at the early stage of elongation.

SIGNOR-271747

P53350

Q96EP1

0

polyubiquitination

down-regulates quantity by destabilization

0.468

Chfr, a mitotic stress checkpoint, plays an important role in cell cycle progression, tumor suppression and the processes that require the E3 ubiquitin ligase activity mediated by the RING finger domain. Chfr stimulates the formation of polyubiquitin chains by ub-conjugating enzymes, and induces the proteasome-dependent degradation of a number of cellular proteins including Plk1 and Aurora A.

SIGNOR-271464

P37840

P68400

0

phosphorylation

up-regulates

0.514

In vitro experiments and two-dimensional phosphopeptide mapping provided further evidence that serine 129 was phosphorylated by ck-1 and ck-2. Moreover, phosphorylation of serine 129 was reduced in vivo upon inhibition of ck-1 or ck-2. These data demonstrate that alpha-synuclein is constitutively phosphorylated within its c terminus and may indicate that the function of alpha-synuclein is regulated by phosphorylation/dephosphorylation.From these data we conclude that _-synuclein is predominantly phosphorylated at serine residue 129. However, a second serine at position 87 is also used for phosphorylation to some extent. together, these data may indicate that ck-1 and ck-2 are involved in the regulation of neuronal function and one may speculate that phosphorylation of _-synuclein could affect its binding to membranes.

SIGNOR-73807

P31629

P30874

1

transcriptional regulation

up-regulates quantity by expression

0.411

Activation of somatostatin receptor II expression by transcription factors MIBP1 and SEF-2 in the murine brain.

SIGNOR-261617