GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
O00141	P42568	1	phosphorylation	down-regulates activity	0.509	In addition to Nedd4-2, Sgk1 also phosphorylates Af9, forkhead like transcription factor FOXO3a and several other substrates.\|Sgk1 impairs the ability of Af9 to interact with Dot1a at these subregions without impacting Af9 DNA binding activity, leading to targeted histone H3 K79 hypomethylation.	SIGNOR-279111
P01903	Q12986	0	transcriptional regulation	down-regulates quantity by repression	0.396	A novel cysteine-rich sequence-specific DNA-binding protein interacts with the conserved X-box motif of the human major histocompatibility complex class II genes via a repeated Cys-His domain and functions as a transcriptional repressor	SIGNOR-266224
Q96J02	P45983	0	phosphorylation	up-regulates activity	0.654	Itch undergoes JNK1-mediated phosphorylation that greatly enhances its enzymatic activity. To investigate how phosphorylation activates an E3 Ub ligase we have identified the JNK1 phosphorylation sites within Itch as S199, S232, and T222	SIGNOR-245323
A8MUP2	O75390	1	methylation	down-regulates activity	0.2	A mitochondrial matrix-located methyltransferase, methyltransferase-like protein 12 (METTL12), has been reported to methylate CS on the lysine 368 (K368) [15] and K395 residues [16] which are near the active site of CS. The methylation on K395 inhibits CS activity, which can be antagonized by its substrate oxaloacetate.	SIGNOR-267638
Q9BXM7	O95202	1	phosphorylation	up-regulates activity	0.358	Here we demonstrate that PINK1 directly interacts with and phosphorylates LETM1 at Thr192 in vitro.\|Phosphorylated LETM1 or the phospho-mimetic LETM1-T192E increase calcium release in artificial liposomes and facilitates calcium transport in intact mitochondria.	SIGNOR-262540
P27361	P55211	1	phosphorylation	down-regulates activity	0.535	Inhibition of caspase-9 through phosphorylation at thr 125 by erk mapk	SIGNOR-101548
Q13535	P30304	1	phosphorylation	down-regulates activity	0.643	ATR and CHK1 mediated loss of CDC25A activity suspends CDKs, such as CDK2, in an inactive phosphorylated state, blocking initiation of DNA replication origins.\|In the presence of replication stalling, activated CHK1 and ATR phosphorylates CDC25A and promotes its degradation.	SIGNOR-280183
P15692	Q9ULU4	0	transcriptional regulation	down-regulates quantity by repression	0.2	Our quantitative ChIP experiments confirmed that ZMYND8 and JARID1D were co-localized at Slug, CD44, VEGFA, and EGFR genes (Figures 4F–4I). Our ChIP results also showed that ZMYND8 repressed and occupied other JARID1D target genes, such as the matrix metalloproteinase 1 (MMP1) and MMP3, that we previously reported	SIGNOR-262041
P06213	Q99704	1	phosphorylation	up-regulates activity	0.562	Insulin receptor-mediated p62dok tyrosine phosphorylation at residues 362 and 398. p62(dok) is a direct substrate for the IR tyrosine kinase and that phosphorylation at Tyr(362) and Tyr(398) plays an essential role for p62(dok) to interact with its effectors and negatively regulate the insulin signaling pathway.	SIGNOR-251307
P35222	P45984	0	phosphorylation	up-regulates	0.671	Beta-catenin, upon entering the nucleus, in turn activates transcription of downstream target genes. Jnk2 phosphorylates Beta-catenin on critical residues (ser191 and ser605). Jnk activity is required for Beta-catenin nuclear localization in response to wnt.	SIGNOR-178258
P07288	P12272	1	cleavage	down-regulates activity	0.422	Our study demonstrates that PTHrP is a substrate for PSA. The cleavage of the amino-terminal portion of PTHrP completely disrupts its ability to interact with the PTH/PTHrP receptor and thus inhibits its PTH-like activity. \| Our data show that PSA proteolytically cleaves PTHrP (1-34) after either residue 22 or 23, generating three peptide fragments.	SIGNOR-270547
Q13136	P10586	1	relocalization	up-regulates activity	0.8	We have identified a novel cytoplasmic 160 kDa phosphoserine protein termed LAR-interacting protein 1 (LIP.1), which binds to the LAR membrane-distal D2 protein tyrosine phosphatase domain and appears to localize LAR to focal adhesions.	SIGNOR-264141
Q14185	P00533	0	phosphorylation	up-regulates activity	0.308	Here we report that EGFRvIII induces serine phosphorylation at serine residue 1250 (S1250) of Dock180 (p-Dock180 S1250 ) and that p-Dock180 S1250 is required for EGFRvIII-promoted Rac1 activation, glioblastoma cell growth, survival and invasion in vitro and in vivo .\|We demonstrate that EGFRvIII induces serine phosphorylation of Dock180, stimulates Rac1 activation and glioma cell migration.	SIGNOR-279329
P14598	Q9NWZ3	0	phosphorylation	up-regulates	0.38	Phosphorylation of the cytosolic factor p47phox is essential for activation of the nadph oxidase.We found that thr133, ser288 and thr356, targets for irak-4 phosphorylation in vitro, are also phosphorylated in endogenous p47phox after lps stimulation. We conclude that irak-4 phosphorylates p47phox and regulates nadph oxidase activation after lps stimulation.	SIGNOR-152027
Q8WYL5	O94806	0	phosphorylation	down-regulates activity	0.286	Active PKD Isoforms Phosphorylate and Inactivate SSH1L\|Here, we show that active PKD3 also mediates SSH1L phosphorylation at Ser-978 and binding to 14-3-3, further confirming the involvement of all three PKD isoforms in negatively regulating this phosphatase	SIGNOR-275938
P35712	Q00535	0	phosphorylation	down-regulates quantity	0.366	GST-Sox6 was phosphorylated in vitro by Cdk5 and p35 (XREF_FIG).\|Inhibition of Cdk5 activity by DN Cdk5 and roscovitine increases the Sox6 expression in primary cortical neurons.	SIGNOR-279365
P13569	P68400	0	phosphorylation	down-regulates	0.278	Cftr possesses two ck2 phosphorylation sites (s422 and t1471) the t1471 residue, previously described as a site for cftr phosphorylation by ck2 (25), seems to be critical for cftr turnover and processing.	SIGNOR-176627
O95243	O15528	1	transcriptional regulation	up-regulates quantity by expression	0.377	Phosphorylation of MBD4 promotes 5-meC glycosylase activity Further evidence emerged to support the involvement of MBD4 in active demethylation. Protein-kinase C phosphorylation of MBD4 at two specific serine residues (165 and 262) following parathyroid hormone stimulation was shown to promote demethylation within the CYP27B1 gene promoter [12]	SIGNOR-275682
Q92918	Q16584	1	phosphorylation	up-regulates	0.574	Hpk1 also phosphorylated mlk-3 activation loop in vitro, and ser281 was found to be the major phosphorylation site, indicating that hpk1 also activates mlk-3 via phosphorylation of the kinase activation loop.	SIGNOR-83415
P68400	P30307	1	phosphorylation	down-regulates	0.302	Inhibition of protein kinase ck2 enzyme activity in vivo resulted in an enhanced nuclear localization of cdc25c. Thus, phosphorylation of cdc25c at threonine 236 is an important signal for the retention of cdc25c in the cytoplasm	SIGNOR-123713
Q8ND25	Q03135	1	polyubiquitination	down-regulates quantity by destabilization	0.364	The ubiquitin ligase ZNRF1 promotes caveolin-1 ubiquitination and degradation to modulate inflammation. ZNRF1 mediates CAV1 polyubiquitination at lysine 39 and promote CAV1 degradation to modulate TLR4-mediated immune response.	SIGNOR-272327
P41743	Q9H8V3	1	phosphorylation	up-regulates	0.474	Our data support a model in which pkc?-Mediated phosphorylation regulates ect2 binding to the oncogenic pkc?-Par6 complex thereby activating rac1 activity and driving transformed growth and invasion.	SIGNOR-170790
O15530	P30559	1	phosphorylation	up-regulates activity	0.2	We found that Ser261 in OXTR was phosphorylated by protein kinase D1 (PKD1).\|In HEK293A cells, the PKD1-mediated phosphorylation of OXTR promoted its binding to Gq protein and, in turn, OXTR-mediated phosphorylation of PKD1, indicating a positive feedback loop.	SIGNOR-268577
P06241	P20916	1	phosphorylation	up-regulates activity	0.425	Fyn constitutively binds to MAG in a latent form. Ligand stimulation of L-MAG would result in activation of Fyn kinase and phosphorylation of Tyr-620. Binding and activation of PLC y through this phosphotyrosine residue would contribute to the signaling pathway involved in the regulation of myelination.	SIGNOR-251178
Q9UBK2	O14793	1	transcriptional regulation	down-regulates quantity by repression	0.361	PGC-1 alpha specifically induces IGF1 and represses myostatin, and expression of PGC-1a 4 in vitro and in vivo induces robust skeletal muscle hypertrophy	SIGNOR-256151
Q13976	P35367	1	phosphorylation	down-regulates	0.2	Ser396 and ser398 are also potential phosphorylation sites for capk, cgmp-dependent protein kinase, and camk ii. Elevation of intracellular camp content has been shown to attenuate histamine-induced accumulation of ip in c6 glioma cells (peakman and hill, 1994) and in ddt1 mf-2 smooth muscle cells (sipma et al., 1995	SIGNOR-66019
Q9HC98	O00141	1	phosphorylation	up-regulates activity	0.338	The present study is the first report of a protein kinase (NEK6) capable of phosphorylating the hydrophobic motif of SGK1, although our data suggest that NEK6 may not mediate this reaction in cells. Nevertheless, the phosphorylation of the hydrophobic motif of SGK1in vitro, coupled with the phosphorylation of the T-loop with PDK1, may be a useful way of generating fully active wild type SGK1. Ser377 and Ser422of SGK1, and the CDK7 T-loop peptide, which are phosphorylated by NEK6.	SIGNOR-250297
P62140	Q13422	1	dephosphorylation	up-regulates	0.265	Ikarosis dephosphorylated by protein phosphatase 1 (pp1) via interaction at a consensus pp1-binding motif/ hyperphosphorylation of ikaros promotes its degradation by the ubiquitin/proteasome pathway	SIGNOR-174862
P52747	P17987	1	transcriptional regulation	up-regulates quantity by expression	0.279	The transcription from the minimalCcta promoter was up-regulated 3-fold by ZNF143 and 6-fold by ZNF76 when full-length proteins were co-expressed, indicating that both ZNF143 and ZNF76 can enhance Ccta transcription.	SIGNOR-266220
P17612	Q9Y6X9	1	phosphorylation	up-regulates quantity by stabilization	0.2	Mechanistically, GPER1 activates PRKACA (protein kinase cAMP-activated catalytic subunit alpha), which in turn phosphorylates MORC2 at threonine 582 (T582). Phosphorylated MORC2 decreases its interaction with HSPA8 (heat shock protein family A [Hsp70] member 8) and LAMP2A (lysosomal associated membrane protein 2A), two core components of the chaperone-mediated autophagy (CMA) machinery, thus protecting MORC2 from lysosomal degradation by CMA.	SIGNOR-273781
P06213	Q05209	0	dephosphorylation	down-regulates	0.378	Interestingly, all PTPs that were tested could completely dephosphorylate the receptor, given sufficient time, including a negative control (PTP-PEST) that failed to bind IRK as a trapping mutant.	SIGNOR-75894
P42336	P09493	1	phosphorylation	up-regulates activity	0.2	Here, we demonstrate a requirement for the protein kinase activity of PI(3)K in agonist-dependent beta-adrenergic receptor (betaAR) internalization. Using PI(3)K mutants with either protein or lipid phosphorylation activity, we identify the cytoskeletal protein non-muscle tropomyosin as a substrate of PI(3)K, which is phosphorylated in a wortmannin-sensitive manner on residue Ser 61. A constitutively dephosphorylated (S61A) tropomyosin mutant blocks agonist-dependent betaAR internalization, whereas a tropomyosin mutant that mimics constitutive phosphorylation (S61D) complements the PI(3)K mutant, with only lipid phosphorylation activity reversing the defective betaAR internalization.	SIGNOR-263027
P60484	Q13464	0	phosphorylation	up-regulates	0.656	In addition, active rhoa is able to stimulate the phospholipid phosphatase activity of pten in human embryonic kidney cells and leukocytes, and this regulation seems to require rhoa's downstream effector, rhoa-associated kinase (rock). together with the observation that individual substitution of ser 229 and thr 223 restored some of the rescuing ability (fig. 4b), we conclude that effective regulation of pten by sdf-1 may require more than one of these residues.	SIGNOR-134855
Q01974	P49674	0	phosphorylation	up-regulates	0.268	We also show that ror2 is phosphorylated by ckiepsilon on serine/threonine residues.	SIGNOR-129117
Q9H6Z9	P07550	1	hydroxylation	up-regulates quantity by stabilization	0.318	We further show that the interaction of pVHL with beta(2)AR is dependent on proline hydroxylation (proline-382 and -395) and that the dioxygenase EGLN3 interacts directly with the beta(2)AR to serve as an endogenous beta(2)AR prolyl hydroxylase. Under hypoxic conditions, receptor hydroxylation and subsequent ubiquitylation decrease dramatically, thus attenuating receptor degradation and down-regulation.	SIGNOR-262007
P00519	Q96MU7	1	phosphorylation	down-regulates	0.305	We show that yt521-b is tyrosine phosphorylated by c-abl in the nucleus.We propose that tyrosine phosphorylation causes sequestration of YT521-B in an insoluble nuclear form, which abolishes the ability of YT521-B to change alternative splice sites.	SIGNOR-125167
P0CG47	P45974	0	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
P09211	P17252	0	phosphorylation	up-regulates activity	0.2	Peptide phosphorylation analyses and both phosphorylation and enzyme kinetic studies with GSTP1 proteins mutated at candidate amino acid residues established Ser-42 and Ser-184 as putative phospho-acceptor residues for both kinases in the GSTP1 protein. Together, these findings show PKA- and PKC-dependent phosphorylation as a significant post-translational mechanism of regulation of GSTP1 function. Together, these results further support S42 and S184 as major phosphor-acceptor residues for PKA and PKC and suggest that the increased activity of the phospho-GSTP1 was not simply a consequence of the negative charge introduced in the GSTP1 protein by the phosphate group.All eight PKC isoforms, PKC-α, PKC-βI, PKC-βII, PKC-ε, PKC-γ, PKC-η, and PKC-ζ phosphorylated the GSTP1 protein efficiently	SIGNOR-276024
Q9H2X6	Q15038	1	phosphorylation	down-regulates activity	0.2	In response to DNA damage, HIPK2 phosphorylates DAZAP2 at several Ser/Thr residues including Ser77, which inhibits its HIPK2-degrading function and targets it to the cell nucleus.	SIGNOR-279335
O00308	Q01860	1	ubiquitination	down-regulates quantity	0.453	WWP2 promotes degradation of transcription factor OCT4 in human embryonic stem cells\|Here, we report that human WWP2, an E3 ubiquitin (Ub)-protein ligase, interacts with OCT4 specifically through its WW domain and enhances Ub modification of OCT4 both in vitro and in vivo.	SIGNOR-268850
O75385	P46937	1	phosphorylation	up-regulates quantity by stabilization	0.2	Mechanistically, hypoxia stimulates ULK1 to translocate into nucleus, where it interacts with and phosphorylates yes-associated protein (YAP) at Ser227, resulting in YAP stabilization through blockade of ubiquitin-proteasome system (UPS), which in turn facilitates PKM2 transcription, glycolysis, cell proliferation in vitro as well as PDAC growth in mice.	SIGNOR-277570
P61978	P12931	0	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
P10636-2	Q7KZI7	0	phosphorylation	down-regulates activity	0.707	We have studied the relationship between the phosphorylation oftau by several kinases (MARK, PKA, MAPK, GSK3) and its assembly into PHFs. By contrast, MARK and PKA phosphorylate several sites within the repeats (notably theKXGS motifs including Ser262, Ser324, and Ser356, plus Ser320); in addition PKA phosphorylates somesites in the flanking domains, notably Ser214. This type of phosphorylation strongly reduces tau’s affinityfor microtubules, and at the same time inhibits tau’s assembly into PHFs.	SIGNOR-275437
P48729	P12830	1	phosphorylation	down-regulates activity	0.312	Casein kinase 1 is a novel negative regulator of E-cadherin-based cell-cell contacts\|CK1 colocalizes with E-cadherin and phosphorylates the cytoplasmic domain of E-cadherin in vitro and in a cell culture system. We show that the major CK1 phosphorylation site of E-cadherin is serine 846	SIGNOR-274045
P10071	Q6PHR2	0	phosphorylation	up-regulates activity	0.561	We show that ULK3 is able to phosphorylate three mammalian GLI proteins in vitro	SIGNOR-260799
P16519	P01178-PRO_0000020496	1	cleavage	up-regulates quantity	0.2	Oxytocin-extended form is further cleaved by enzymatic activity to yield the nine-amino-acid active peptide, OT. The proteolysis may involve several pro-hormone convertases, convertase 2 (PC2) (20p11-1-11.2) and convertase 5 (PC5) (9q21.3) (Gabreels et al 1998). Both enzymes are found in OT neurosecretory vesicles and are a part of a family of subtilisen/kexinlike convertases (Seidah et al 1994). It is a product of the OT gene located at human gene locus 20p13 (Rao et al 1992). The processing cascade results in the production of neurophysin I and OT extended form (OT-X), which is OT with a C-terminal, three-amino-acid extension.	SIGNOR-270337
Q9Y478	Q8IYT8	0	phosphorylation	down-regulates	0.329	Ulk1/2 in turn phosphorylates all three subunits of ampk and thereby negatively regulates its activity	SIGNOR-173092
Q13263	P12931	0	phosphorylation	down-regulates activity	0.2	Among SFKs, Src strongly induces tyrosine phosphorylation of KAP1.\|Immunostaining and chromatin fractionation show that Src and Lyn decrease the association of KAP1 with heterochromatin in a kinase activity-dependent manner.	SIGNOR-280137
Q01130	Q9UBN7	0	deacetylation	up-regulates	0.356	Our data support a model in which hdac6 has a key role in the maintenance of srsf2 protein level by inhibiting tip60_mediated acetylation and proteasomal degradation.	SIGNOR-170590
P22059	Q15139	0	phosphorylation	down-regulates	0.444	Pkd attenuates the function of both cert and osbp by phosphorylation at their respective ser(132) and ser(240) residues (phosphorylation inhibition)	SIGNOR-171756
Q05655	P29353	1	phosphorylation	up-regulates	0.569	Pkc delta phosphorylates p52shca at ser29 to regulate erk activation in response to h2o2.	SIGNOR-149398
O00410	O60469	1	relocalization	up-regulates activity	0.2	DSCAM and DSCAML1 specifically interacted with the importin beta IPO5, whereas deletion of the identified NLSs abolished this specific interaction and suppressed nuclear translocation of the DSCAM/L1 ICDs in cell lines and cultured neurons. This suggests a direct role of IPO5 in the nuclear import of the DSCAM/L1 ICDs.	SIGNOR-264273
P12931	Q13480	1	phosphorylation	up-regulates	0.704	Using both mutagenesis and mass spectrometry approaches, y242, y259, y317, y373 and y627 of gab1 were identified to be phosphorylated by c-src a gab1 mutant with substitutions of the src phosphorylation sites failed to promote hgf-induced dna synthesis	SIGNOR-236314
Q04864	O14920	0	phosphorylation	up-regulates activity	0.62	We are the first to identify Ser484 and Ser494 as the major sites of in vitro phosphorylation of REL by IKKalpha and IKKbeta.	SIGNOR-279620
Q16821	P13807	1	dephosphorylation	up-regulates	0.502	In skeletal muscle, the activation of glycogen synthase by insulin involves the dephosphorylation of serine residues that are phosphorylated by gsk3 and dephosphorylated by the glycogen-associated form of protein phosphatase-l (pp1g).	SIGNOR-37301
P06493	Q9UKT4	1	phosphorylation	down-regulates quantity by destabilization	0.753	We find that both Emi1 phosphorylation by cyclin and Cdc2 and phosphorylation on a consensus site (DSGxxS) direct recruitment of betaTrCP and subsequent Emi1 ubiquitination and destruction.	SIGNOR-279143
O94759	P17252	0	phosphorylation	up-regulates activity	0.2	ROS production in endothelial cells or directly applying ROS induced PKC\u03b1 activation and phosphorylation of TRPM2 at Ser 39.\|ROS production in endothelial cells or directly applying ROS induced PKCalpha activation and phosphorylation of TRPM2 at Ser 39.	SIGNOR-280082
P27361	Q02548	1	phosphorylation	down-regulates activity	0.247	In this study, we demonstrated that PAX5 was phosphorylated by ERK1/2 in vitro and in vivo at serines 189 and 283. This phosphorylation attenuated the transcriptional repression of BLIMP1 by PAX5.	SIGNOR-269086
Q96T51	P51813	0	phosphorylation	up-regulates activity	0.634	Etk interacts with RUFY1 through its SH3 and SH2 domains. RUFY1 is tyrosine-phosphorylated and appears to be a substrate of Etk. Phosphorylation of the two tyrosine residues, Tyr-281 and Tyr-292, located in the linker region of the two coiled-coil domains by Etk seems to be critical for RUFY1 targeting to the endosomes.	SIGNOR-262679
O00418	Q16539	0	phosphorylation	down-regulates activity	0.334	Inhibition of eEF2 kinase resulting from phosphorylation of Ser-396 by SAPK2a p38 was approx.25%.	SIGNOR-249707
Q15418	Q9HC62	1	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
P23677	Q9UQM7	0	phosphorylation	up-regulates	0.329	D-myo-inositol 1,4,5-trisphosphate 3-kinase a is activated by receptor activation through a calcium:calmodulin-dependent protein kinase ii phosphorylation mechanism. the phosphorylated residue was thr311.	SIGNOR-48387
Q9Y4L5	P00533	1	polyubiquitination	down-regulates quantity by destabilization	0.375	RNF126 and Rabring7 associate with the EGFR through a ubiquitin-binding zinc finger domain and both E3 ubiquitin ligases promote ubiquitylation of EGFR. In HeLa cells depleted of either RNF126 or Rabring7 the EGFR is retained in a late endocytic compartment and is inefficiently degraded.	SIGNOR-272104
Q07955	P21127	0	phosphorylation	up-regulates activity	0.283	In comparison, CLK1 expression leads to speckle dissolution and diffuse GFP-SRSF1 localization in the nucleus.\|We showed that CLK1 phosphorylates SRSF1 at approximately 18 sites inducing a gel shift from 35 to about 38 kDa on SDS-PAGE (XREF_FIG, upper panel).	SIGNOR-279499
P11309	O95644	1	phosphorylation	up-regulates activity	0.643	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-276775
Q15942	P06493	0	phosphorylation	up-regulates activity	0.309	As predicted by our hypothesis, the Cdc2 dependent phosphorylation has been shown to allow the full-length zyxin to interact with h-warts and LATS1 (XREF_FIG A).\|Phosphorylation of Zyxin by Cdc2 Regulates Binding to h-warts and LATS1.	SIGNOR-279498
P18848	Q9Y2Z4	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-269432
P24941	Q13118	1	phosphorylation	up-regulates quantity	0.329	In this study we have shown that CDK2 phosphorylates KLF10 at residue Ser 206 in vivo and in vitro .\|In this study, we have shown that KLF10 protein has tightly controlled expression and that the expression level varies in a cell cycle dependent manner whereby CDK2 up-regulates activity the protein level of KLF10 through interference with the protein 's association with SIAH1.	SIGNOR-278394
P62826	Q9NRC8	0	deacetylation	down-regulates activity	0.2	N this study, we demonstrated that SIRT7 interacts with a small GTPase, Ras-related nuclear antigen (Ran), and deacetylates Ran at K37. \|The nuclear export by CRM1 requires an interaction with the small GTPase Ras-related nuclear antigen (Ran), which cycles between GTP- and GDP-bound states. The binding of Ran GTP to CRM1 in the nucleus increases the affinity of CRM1 for cargo proteins [[18], [19], [20]]. Interestingly, Ran is a lysine-acetylated protein	SIGNOR-275849
Q06124	Q15116	1	dephosphorylation	down-regulates activity	0.659	Related to the latter notion, we recently showed that SHP2 dephosphorylates PD-1 to disassemble the PD-1:SHP2 complex ( xref ).	SIGNOR-277052
Q68DK7	Q16778	1	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-271977
Q8IVP5	Q96HS1	0	dephosphorylation	up-regulates activity	0.627	Here, we identify that the mitochondrially localized PGAM5 phosphatase interacts with and dephosphorylates FUNDC1 at serine 13 (Ser-13) upon hypoxia or carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP) treatment. Dephosphorylation of FUNDC1 catalyzed by PGAM5 enhances its interaction with LC3, which is abrogated following knockdown of PGAM5 or the introduction of a cell-permeable unphosphorylated peptide encompassing the Ser-13 and LIR of FUNDC1. We further observed that CK2 phosphorylates FUNDC1 to reverse the effect of PGAM5 in mitophagy activation.	SIGNOR-273654
Q99683	Q9H2G2	0	phosphorylation	up-regulates	0.253	Induction of apoptosis by the ste20-like kinase slk, a germinal center kinase that activates apoptosis signal-regulating kinase and p38	SIGNOR-142665
Q9UPN4	O00444	0	phosphorylation	up-regulates activity	0.534	We conclude that PLK4 phosphorylates CEP131 at Ser 78 to maintains centriolar satellite integrity.	SIGNOR-280075
Q15465	Q5VTY9	0	palmitoylation	up-regulates	0.683	Our molecular analysis of knockout mice deficient in skn, the murine homolog of the drosophila ski gene, which catalyzes hh palmitoylation, and gene-targeted mice producting a non palmitoylated form of shh indicates that hh palmitoylation is essential for its activity as well as the generation of a protein gradient in the developing embryos	SIGNOR-124118
P19525	Q9H3R0	1	phosphorylation	down-regulates quantity by destabilization	0.2	In the absence of Wnt3a, protein kinase R phosphorylated KDM4C at Ser918, inducing KDM4C ubiquitination and degradation.	SIGNOR-277497
Q96FF9	P06493	0	phosphorylation	down-regulates activity	0.711	Here we show that the mitotic kinases Aurora B and Cyclin-dependent kinase 1 (Cdk1) destabilize interactions between Sororin and the cohesin subunit precocious dissociation of sisters protein 5 (Pds5) by phosphorylating Sororin, leading to release of acetylated cohesin from chromosome arms and loss of cohesion.	SIGNOR-276118
P17252	Q9H3Q1	1	phosphorylation	down-regulates activity	0.2	Cdc42 effector protein-4 (CEP4) was recently identified by our laboratory to be a substrate of multiple PKC isoforms in non-transformed MCF-10A human breast cells. MS/MS analysis verified that Ser(18) and Ser(80) were directly phosphorylated by PKCα in vitro. Phosphorylation of CEP4 severely diminished its affinity for Cdc42 while promoting Rac activation and formation of filopodia (microspikes).	SIGNOR-263160
Q96JA1	Q15303	1	ubiquitination	down-regulates	0.608	We report upregulation of lrig1 transcript and protein upon egf stimulation, and physical association of the encoded protein with the four egfr orthologs of mammals. Upregulation of lrig1 is followed by enhanced ubiquitylation and degradation of egfr. The underlying mechanism involves recruitment of c-cbl, an e3 ubiquitin ligase that simultaneously ubiquitylates egfr and lrig1 and sorts them for degradation.	SIGNOR-139954
O00327	P35398	0	transcriptional regulation	up-regulates quantity by expression	0.689	Direct Regulation of the NPAS2 Promoter by RORα and REV-ERBα. it appears in the context of the NPAS2 promoter RORα functions as a transcriptional activator, but REV-ERBα may only function as an inhibitor of RORα activity by blocking binding.	SIGNOR-267982
P08195	Q5T0T0	0	polyubiquitination	down-regulates quantity by destabilization	0.2	Taken together, these findings demonstrate that MARCH8 directly ubiquitinates CD98, and this likely leads to its routing to late endosomes for degradation.	SIGNOR-272755
P38398	O96017	0	phosphorylation	up-regulates	0.787	In this study, we tested the hypothesis that the brca1-mediated regulation of recombination requires the chk2- and atm-dependent phosphorylation sites.	SIGNOR-120575
P68400	P78344	1	phosphorylation	up-regulates activity	0.226	DAP5(S902) is phosphorylated by CK2α. Phosphorylation of DAP5(S902) by CK2α is required for eIF2β binding.	SIGNOR-266384
P45984	Q9UIG0	1	phosphorylation	up-regulates	0.2	Wstf, a specific component of two chromatin remodeling complexes (swi/snf-type winac and iswi-type wich), was phosphorylated by the stimulation of mapk cascades in vitro and in vivo. Ser-158 residue in the wac (wstf/acf1/cbpq46) domain, located close to the n terminus of wstf, was identified as a major phosphorylation target	SIGNOR-188168
P40763	Q16827	0	dephosphorylation	down-regulates activity	0.376	In addition, this group found that PTPRO dephosphorylated STAT3 at Y705 and S727 then attenuated STAT3 signalling.	SIGNOR-277062
Q9HAU4	O95630	1	polyubiquitination	down-regulates quantity by destabilization	0.529	RNF11 recruits AMSH to Smurf2 E3 ligase. Smurf2 promotes ubiquitination of AMSH in the presence of wt RNF11. Previously, we have shown that RNF11 interacts with the HECT-type E3 ligases AIP4 and Smurf2. Here, we show that RNF11 binds to AMSH in mammalian cells and that this interaction is independent of the RNF11 RING-finger domain and the PY motif. Our results also demonstrate that AMSH is ubiquitinated by Smurf2 E3 ligase in the presence of RNF11 and that a consequent reduction in its steady-state level requires both RNF11 and Smurf2. RNF11 therefore recruits AMSH to Smurf2 for ubiquitination, leading to its degradation by the 26S proteasome.	SIGNOR-272951
Q969T9	P07947	0	phosphorylation	up-regulates activity	0.304	Using dominant-negative, constitutively active mutants, RNAi, and pharmacological studies, we demonstrated that phosphorylation of WBP2 at Tyr192 and Tyr231 could be regulated by c-Src and c-Yes kinases.We further showed that abrogating WBP2 phosphorylation impaired >60% of ERα reporter activity, putatively by blocking nuclear entry of WBP2 and its interaction with ERα.	SIGNOR-273582
P10912	P17706	0	dephosphorylation	down-regulates activity	0.295	PTPH1 only bound Tyr534, whereas PTP1B and TC-PTP bound multiple phosphopeptides. Earlier work suggests that Tyr332, Tyr487, Tyr534, Tyr566, and Tyr627 are all phosphorylated after GH stimulation (21). Apart from Tyr627, all of these also appear good PTP substrates	SIGNOR-248394
Q92831	P0DPK5	1	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-269615
P09630	P04271	1	transcriptional regulation	up-regulates quantity by expression	0.2	HOXC6 and HOXC11 increase transcription of S100beta gene in BrdU-induced in vitro differentiation of GOTO neuroblastoma cells into Schwannian cells.	SIGNOR-261646
P46019	P22694	0	phosphorylation	down-regulates activity	0.325	Phosphorylation of the alpha and beta subunits by the 3',5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) also relieves inhibition of the gamma subunit and thereby activates the enzyme.	SIGNOR-267412
Q8IYT8	P19367	1	phosphorylation	up-regulates activity	0.2	Here, we demonstrate that, during deprivation of amino acid and growth factors, ULK1/2 directly phosphorylate key glycolytic enzymes including hexokinase (HK), phosphofructokinase 1 (PFK1), enolase 1 (ENO1), and the gluconeogenic enzyme fructose-1,6-bisphosphatase (FBP1).Phosphorylation of these enzymes leads to enhanced HK activity to sustain glucose uptake but reduced activity of FBP1 to block the gluconeogenic route and reduced activity of PFK1 and ENO1 to moderate drop of glucose-6-phosphate and to repartition more carbon flux to pentose phosphate pathway (PPP), maintaining cellular energy and redox homeostasis at cellular and organismal levels.Similar results were also obtained using ULK2 as the kinase (data not shown).	SIGNOR-274042
O60260	P42566	1	ubiquitination	up-regulates	0.2	Treatment of cells with egf stimulates parkin binding to both eps15 and the egfr and promotes parkin-mediated ubiquitination of eps15	SIGNOR-148218
P10070	P49841	0	phosphorylation	down-regulates quantity by destabilization	0.562	The degradation of Gli2 requires the phosphorylation of a cluster of numerous serine residues in its carboxyl terminus by protein kinase A and subsequently by casein kinase 1 and glycogen synthase kinase 3.	SIGNOR-249590
O14964	Q7Z6J0	0	ubiquitination	down-regulates quantity	0.246	Importantly, ubiquitination of Hrs mediated by POSH caused the reduction of Hrs level via the ubiquitin-proteasome pathway.	SIGNOR-278575
P04637	Q96Q15	0	phosphorylation	up-regulates	0.411	Hsmg-1 is a stress-activated kinase that phosphorylates p53 and hupf1 in vitrothe observation that hsmg-1 exhibits p53 (ser-15) kinase activity in vitro suggested that this pikk might be involved in genotoxic stress-induced p53 phosphorylation and stabilization in intact cells.	SIGNOR-125135
O15217	P0DMV9	0	relocalization	up-regulates activity	0.2	Model showing Ser189/Thr193 protein kinase dependent phosphorylation of GST A4‐4 has increased affinity for chaperone Hsp70 which activates mitochondrial competent import signals for GSTA4‐4. \|Protein kinase A mediated phosphorylation of serine residues of CYPs increases the affinity of proteins for binding to cytoplasmic chaperones such as heat shock proteins (Hsp), Hsp70/Hsp90, resulting in increased mitochondrial translocation	SIGNOR-264800
P30304	P49137	0	phosphorylation	down-regulates	0.364	Mk2 was required for the degradation of cdc25a. Mk2 phosphorylates cdc25a in vitro. Phosphorylation of cdc25a in vivo has been shown to facilitate its ubiquitin-mediated proteolysis	SIGNOR-152996
Q14145	Q9NY33	0	cleavage	down-regulates quantity by destabilization	0.599	The influence of DPP3 on the Keap1-Nrf2/ARE signal pathway suggest a direct involvement of DPP3 in the oxidative stress response [8,14,31,53,99,100]. It was shown that DPP3 competes with Nrf2 through the ETGE motif to bind to Keap1 and consequently enhances the translocation of Nrf2 to the nucleus, thereby driving the expression of an array of genes encoding antioxidative enzymes [99]. More specifically, binding of DPP3 to Keap1 releases Nrf2, and thus, prevents its degradation through the 26S proteasome	SIGNOR-268464
Q9NS23	P11802	0	phosphorylation	down-regulates	0.409	This skp2-dependent destruction of rassf1a requires phosphorylation of the latter on serine-203 by cyclin d-cyclin-dependent kinase 4.	SIGNOR-159849

O00141

P42568

1

phosphorylation

down-regulates activity

0.509

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

SIGNOR-279111

P01903

Q12986

0

transcriptional regulation

down-regulates quantity by repression

0.396

A novel cysteine-rich sequence-specific DNA-binding protein interacts with the conserved X-box motif of the human major histocompatibility complex class II genes via a repeated Cys-His domain and functions as a transcriptional repressor

SIGNOR-266224

Q96J02

P45983

0

phosphorylation

up-regulates activity

0.654

Itch undergoes JNK1-mediated phosphorylation that greatly enhances its enzymatic activity. To investigate how phosphorylation activates an E3 Ub ligase we have identified the JNK1 phosphorylation sites within Itch as S199, S232, and T222

SIGNOR-245323

A8MUP2

O75390

1

methylation

down-regulates activity

0.2

A mitochondrial matrix-located methyltransferase, methyltransferase-like protein 12 (METTL12), has been reported to methylate CS on the lysine 368 (K368) [15] and K395 residues [16] which are near the active site of CS. The methylation on K395 inhibits CS activity, which can be antagonized by its substrate oxaloacetate.

SIGNOR-267638

Q9BXM7

O95202

1

phosphorylation

up-regulates activity

0.358

Here we demonstrate that PINK1 directly interacts with and phosphorylates LETM1 at Thr192 in vitro.|Phosphorylated LETM1 or the phospho-mimetic LETM1-T192E increase calcium release in artificial liposomes and facilitates calcium transport in intact mitochondria.

SIGNOR-262540

P27361

P55211

1

phosphorylation

down-regulates activity

0.535

Inhibition of caspase-9 through phosphorylation at thr 125 by erk mapk

SIGNOR-101548

Q13535

P30304

1

phosphorylation

down-regulates activity

0.643

ATR and CHK1 mediated loss of CDC25A activity suspends CDKs, such as CDK2, in an inactive phosphorylated state, blocking initiation of DNA replication origins.|In the presence of replication stalling, activated CHK1 and ATR phosphorylates CDC25A and promotes its degradation.

SIGNOR-280183

P15692

Q9ULU4

0

transcriptional regulation

down-regulates quantity by repression

0.2

Our quantitative ChIP experiments confirmed that ZMYND8 and JARID1D were co-localized at Slug, CD44, VEGFA, and EGFR genes (Figures 4F–4I). Our ChIP results also showed that ZMYND8 repressed and occupied other JARID1D target genes, such as the matrix metalloproteinase 1 (MMP1) and MMP3, that we previously reported

SIGNOR-262041

P06213

Q99704

1

phosphorylation

up-regulates activity

0.562

Insulin receptor-mediated p62dok tyrosine phosphorylation at residues 362 and 398. p62(dok) is a direct substrate for the IR tyrosine kinase and that phosphorylation at Tyr(362) and Tyr(398) plays an essential role for p62(dok) to interact with its effectors and negatively regulate the insulin signaling pathway.

SIGNOR-251307

P35222

P45984

0

phosphorylation

up-regulates

0.671

Beta-catenin, upon entering the nucleus, in turn activates transcription of downstream target genes. Jnk2 phosphorylates Beta-catenin on critical residues (ser191 and ser605). Jnk activity is required for Beta-catenin nuclear localization in response to wnt.

SIGNOR-178258

P07288

P12272

1

cleavage

down-regulates activity

0.422

Our study demonstrates that PTHrP is a substrate for PSA. The cleavage of the amino-terminal portion of PTHrP completely disrupts its ability to interact with the PTH/PTHrP receptor and thus inhibits its PTH-like activity. | Our data show that PSA proteolytically cleaves PTHrP (1-34) after either residue 22 or 23, generating three peptide fragments.

SIGNOR-270547

Q13136

P10586

1

relocalization

up-regulates activity

0.8

We have identified a novel cytoplasmic 160 kDa phosphoserine protein termed LAR-interacting protein 1 (LIP.1), which binds to the LAR membrane-distal D2 protein tyrosine phosphatase domain and appears to localize LAR to focal adhesions.

SIGNOR-264141

Q14185

P00533

0

phosphorylation

up-regulates activity

0.308

Here we report that EGFRvIII induces serine phosphorylation at serine residue 1250 (S1250) of Dock180 (p-Dock180 S1250 ) and that p-Dock180 S1250 is required for EGFRvIII-promoted Rac1 activation, glioblastoma cell growth, survival and invasion in vitro and in vivo .|We demonstrate that EGFRvIII induces serine phosphorylation of Dock180, stimulates Rac1 activation and glioma cell migration.

SIGNOR-279329

P14598

Q9NWZ3

0

phosphorylation

up-regulates

0.38

Phosphorylation of the cytosolic factor p47phox is essential for activation of the nadph oxidase.We found that thr133, ser288 and thr356, targets for irak-4 phosphorylation in vitro, are also phosphorylated in endogenous p47phox after lps stimulation. We conclude that irak-4 phosphorylates p47phox and regulates nadph oxidase activation after lps stimulation.

SIGNOR-152027

Q8WYL5

O94806

0

phosphorylation

down-regulates activity

0.286

Active PKD Isoforms Phosphorylate and Inactivate SSH1L|Here, we show that active PKD3 also mediates SSH1L phosphorylation at Ser-978 and binding to 14-3-3, further confirming the involvement of all three PKD isoforms in negatively regulating this phosphatase

SIGNOR-275938

P35712

Q00535

0

phosphorylation

down-regulates quantity

0.366

GST-Sox6 was phosphorylated in vitro by Cdk5 and p35 (XREF_FIG).|Inhibition of Cdk5 activity by DN Cdk5 and roscovitine increases the Sox6 expression in primary cortical neurons.

SIGNOR-279365

P13569

P68400

0

phosphorylation

down-regulates

0.278

Cftr possesses two ck2 phosphorylation sites (s422 and t1471) the t1471 residue, previously described as a site for cftr phosphorylation by ck2 (25), seems to be critical for cftr turnover and processing.

SIGNOR-176627

O95243

O15528

1

transcriptional regulation

up-regulates quantity by expression

0.377

Phosphorylation of MBD4 promotes 5-meC glycosylase activity Further evidence emerged to support the involvement of MBD4 in active demethylation. Protein-kinase C phosphorylation of MBD4 at two specific serine residues (165 and 262) following parathyroid hormone stimulation was shown to promote demethylation within the CYP27B1 gene promoter [12]

SIGNOR-275682

Q92918

Q16584

1

phosphorylation

up-regulates

0.574

Hpk1 also phosphorylated mlk-3 activation loop in vitro, and ser281 was found to be the major phosphorylation site, indicating that hpk1 also activates mlk-3 via phosphorylation of the kinase activation loop.

SIGNOR-83415

P68400

P30307

1

phosphorylation

down-regulates

0.302

Inhibition of protein kinase ck2 enzyme activity in vivo resulted in an enhanced nuclear localization of cdc25c. Thus, phosphorylation of cdc25c at threonine 236 is an important signal for the retention of cdc25c in the cytoplasm

SIGNOR-123713

Q8ND25

Q03135

1

polyubiquitination

down-regulates quantity by destabilization

0.364

The ubiquitin ligase ZNRF1 promotes caveolin-1 ubiquitination and degradation to modulate inflammation. ZNRF1 mediates CAV1 polyubiquitination at lysine 39 and promote CAV1 degradation to modulate TLR4-mediated immune response.

SIGNOR-272327

P41743

Q9H8V3

1

phosphorylation

up-regulates

0.474

Our data support a model in which pkc?-Mediated phosphorylation regulates ect2 binding to the oncogenic pkc?-Par6 complex thereby activating rac1 activity and driving transformed growth and invasion.

SIGNOR-170790

O15530

P30559

1

phosphorylation

up-regulates activity

0.2

We found that Ser261 in OXTR was phosphorylated by protein kinase D1 (PKD1).|In HEK293A cells, the PKD1-mediated phosphorylation of OXTR promoted its binding to Gq protein and, in turn, OXTR-mediated phosphorylation of PKD1, indicating a positive feedback loop.

SIGNOR-268577

P06241

P20916

1

phosphorylation

up-regulates activity

0.425

Fyn constitutively binds to MAG in a latent form. Ligand stimulation of L-MAG would result in activation of Fyn kinase and phosphorylation of Tyr-620. Binding and activation of PLC y through this phosphotyrosine residue would contribute to the signaling pathway involved in the regulation of myelination.

SIGNOR-251178

Q9UBK2

O14793

1

transcriptional regulation

down-regulates quantity by repression

0.361

PGC-1 alpha specifically induces IGF1 and represses myostatin, and expression of PGC-1a 4 in vitro and in vivo induces robust skeletal muscle hypertrophy

SIGNOR-256151

Q13976

P35367

1

phosphorylation

down-regulates

0.2

Ser396 and ser398 are also potential phosphorylation sites for capk, cgmp-dependent protein kinase, and camk ii. Elevation of intracellular camp content has been shown to attenuate histamine-induced accumulation of ip in c6 glioma cells (peakman and hill, 1994) and in ddt1 mf-2 smooth muscle cells (sipma et al., 1995

SIGNOR-66019

Q9HC98

O00141

1

phosphorylation

up-regulates activity

0.338

The present study is the first report of a protein kinase (NEK6) capable of phosphorylating the hydrophobic motif of SGK1, although our data suggest that NEK6 may not mediate this reaction in cells. Nevertheless, the phosphorylation of the hydrophobic motif of SGK1in vitro, coupled with the phosphorylation of the T-loop with PDK1, may be a useful way of generating fully active wild type SGK1. Ser377 and Ser422of SGK1, and the CDK7 T-loop peptide, which are phosphorylated by NEK6.

SIGNOR-250297

P62140

Q13422

1

dephosphorylation

up-regulates

0.265

Ikarosis dephosphorylated by protein phosphatase 1 (pp1) via interaction at a consensus pp1-binding motif/ hyperphosphorylation of ikaros promotes its degradation by the ubiquitin/proteasome pathway

SIGNOR-174862

P52747

P17987

1

transcriptional regulation

up-regulates quantity by expression

0.279

The transcription from the minimalCcta promoter was up-regulated 3-fold by ZNF143 and 6-fold by ZNF76 when full-length proteins were co-expressed, indicating that both ZNF143 and ZNF76 can enhance Ccta transcription.

SIGNOR-266220

P17612

Q9Y6X9

1

phosphorylation

up-regulates quantity by stabilization

0.2

Mechanistically, GPER1 activates PRKACA (protein kinase cAMP-activated catalytic subunit alpha), which in turn phosphorylates MORC2 at threonine 582 (T582). Phosphorylated MORC2 decreases its interaction with HSPA8 (heat shock protein family A [Hsp70] member 8) and LAMP2A (lysosomal associated membrane protein 2A), two core components of the chaperone-mediated autophagy (CMA) machinery, thus protecting MORC2 from lysosomal degradation by CMA.

SIGNOR-273781

P06213

Q05209

0

dephosphorylation

down-regulates

0.378

Interestingly, all PTPs that were tested could completely dephosphorylate the receptor, given sufficient time, including a negative control (PTP-PEST) that failed to bind IRK as a trapping mutant.

SIGNOR-75894

P42336

P09493

1

phosphorylation

up-regulates activity

0.2

Here, we demonstrate a requirement for the protein kinase activity of PI(3)K in agonist-dependent beta-adrenergic receptor (betaAR) internalization. Using PI(3)K mutants with either protein or lipid phosphorylation activity, we identify the cytoskeletal protein non-muscle tropomyosin as a substrate of PI(3)K, which is phosphorylated in a wortmannin-sensitive manner on residue Ser 61. A constitutively dephosphorylated (S61A) tropomyosin mutant blocks agonist-dependent betaAR internalization, whereas a tropomyosin mutant that mimics constitutive phosphorylation (S61D) complements the PI(3)K mutant, with only lipid phosphorylation activity reversing the defective betaAR internalization.

SIGNOR-263027

P60484

Q13464

0

phosphorylation

up-regulates

0.656

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

SIGNOR-134855

Q01974

P49674

0

phosphorylation

up-regulates

0.268

We also show that ror2 is phosphorylated by ckiepsilon on serine/threonine residues.

SIGNOR-129117

Q9H6Z9

P07550

1

hydroxylation

up-regulates quantity by stabilization

0.318

We further show that the interaction of pVHL with beta(2)AR is dependent on proline hydroxylation (proline-382 and -395) and that the dioxygenase EGLN3 interacts directly with the beta(2)AR to serve as an endogenous beta(2)AR prolyl hydroxylase. Under hypoxic conditions, receptor hydroxylation and subsequent ubiquitylation decrease dramatically, thus attenuating receptor degradation and down-regulation.

SIGNOR-262007

P00519

Q96MU7

1

phosphorylation

down-regulates

0.305

We show that yt521-b is tyrosine phosphorylated by c-abl in the nucleus.We propose that tyrosine phosphorylation causes sequestration of YT521-B in an insoluble nuclear form, which abolishes the ability of YT521-B to change alternative splice sites.

SIGNOR-125167

P0CG47

P45974

0

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

P09211

P17252

0

phosphorylation

up-regulates activity

0.2

Peptide phosphorylation analyses and both phosphorylation and enzyme kinetic studies with GSTP1 proteins mutated at candidate amino acid residues established Ser-42 and Ser-184 as putative phospho-acceptor residues for both kinases in the GSTP1 protein. Together, these findings show PKA- and PKC-dependent phosphorylation as a significant post-translational mechanism of regulation of GSTP1 function. Together, these results further support S42 and S184 as major phosphor-acceptor residues for PKA and PKC and suggest that the increased activity of the phospho-GSTP1 was not simply a consequence of the negative charge introduced in the GSTP1 protein by the phosphate group.All eight PKC isoforms, PKC-α, PKC-βI, PKC-βII, PKC-ε, PKC-γ, PKC-η, and PKC-ζ phosphorylated the GSTP1 protein efficiently

SIGNOR-276024

Q9H2X6

Q15038

1

phosphorylation

down-regulates activity

0.2

In response to DNA damage, HIPK2 phosphorylates DAZAP2 at several Ser/Thr residues including Ser77, which inhibits its HIPK2-degrading function and targets it to the cell nucleus.

SIGNOR-279335

O00308

Q01860

1

ubiquitination

down-regulates quantity

0.453

WWP2 promotes degradation of transcription factor OCT4 in human embryonic stem cells|Here, we report that human WWP2, an E3 ubiquitin (Ub)-protein ligase, interacts with OCT4 specifically through its WW domain and enhances Ub modification of OCT4 both in vitro and in vivo.

SIGNOR-268850

O75385

P46937

1

phosphorylation

up-regulates quantity by stabilization

0.2

Mechanistically, hypoxia stimulates ULK1 to translocate into nucleus, where it interacts with and phosphorylates yes-associated protein (YAP) at Ser227, resulting in YAP stabilization through blockade of ubiquitin-proteasome system (UPS), which in turn facilitates PKM2 transcription, glycolysis, cell proliferation in vitro as well as PDAC growth in mice.

SIGNOR-277570

P61978

P12931

0

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

P10636-2

Q7KZI7

0

phosphorylation

down-regulates activity

0.707

We have studied the relationship between the phosphorylation oftau by several kinases (MARK, PKA, MAPK, GSK3) and its assembly into PHFs. By contrast, MARK and PKA phosphorylate several sites within the repeats (notably theKXGS motifs including Ser262, Ser324, and Ser356, plus Ser320); in addition PKA phosphorylates somesites in the flanking domains, notably Ser214. This type of phosphorylation strongly reduces tau’s affinityfor microtubules, and at the same time inhibits tau’s assembly into PHFs.

SIGNOR-275437

P48729

P12830

1

phosphorylation

down-regulates activity

0.312

Casein kinase 1 is a novel negative regulator of E-cadherin-based cell-cell contacts|CK1 colocalizes with E-cadherin and phosphorylates the cytoplasmic domain of E-cadherin in vitro and in a cell culture system. We show that the major CK1 phosphorylation site of E-cadherin is serine 846

SIGNOR-274045

P10071

Q6PHR2

0

phosphorylation

up-regulates activity

0.561

We show that ULK3 is able to phosphorylate three mammalian GLI proteins in vitro

SIGNOR-260799

P16519

P01178-PRO_0000020496

1

cleavage

up-regulates quantity

0.2

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

SIGNOR-270337

Q9Y478

Q8IYT8

0

phosphorylation

down-regulates

0.329

Ulk1/2 in turn phosphorylates all three subunits of ampk and thereby negatively regulates its activity

SIGNOR-173092

Q13263

P12931

0

phosphorylation

down-regulates activity

0.2

Among SFKs, Src strongly induces tyrosine phosphorylation of KAP1.|Immunostaining and chromatin fractionation show that Src and Lyn decrease the association of KAP1 with heterochromatin in a kinase activity-dependent manner.

SIGNOR-280137

Q01130

Q9UBN7

0

deacetylation

up-regulates

0.356

Our data support a model in which hdac6 has a key role in the maintenance of srsf2 protein level by inhibiting tip60_mediated acetylation and proteasomal degradation.

SIGNOR-170590

P22059

Q15139

0

phosphorylation

down-regulates

0.444

Pkd attenuates the function of both cert and osbp by phosphorylation at their respective ser(132) and ser(240) residues (phosphorylation inhibition)

SIGNOR-171756

Q05655

P29353

1

phosphorylation

up-regulates

0.569

Pkc delta phosphorylates p52shca at ser29 to regulate erk activation in response to h2o2.

SIGNOR-149398

O00410

O60469

1

relocalization

up-regulates activity

0.2

DSCAM and DSCAML1 specifically interacted with the importin beta IPO5, whereas deletion of the identified NLSs abolished this specific interaction and suppressed nuclear translocation of the DSCAM/L1 ICDs in cell lines and cultured neurons. This suggests a direct role of IPO5 in the nuclear import of the DSCAM/L1 ICDs.

SIGNOR-264273

P12931

Q13480

1

phosphorylation

up-regulates

0.704

Using both mutagenesis and mass spectrometry approaches, y242, y259, y317, y373 and y627 of gab1 were identified to be phosphorylated by c-src a gab1 mutant with substitutions of the src phosphorylation sites failed to promote hgf-induced dna synthesis

SIGNOR-236314

Q04864

O14920

0

phosphorylation

up-regulates activity

0.62

We are the first to identify Ser484 and Ser494 as the major sites of in vitro phosphorylation of REL by IKKalpha and IKKbeta.

SIGNOR-279620

Q16821

P13807

1

dephosphorylation

up-regulates

0.502

In skeletal muscle, the activation of glycogen synthase by insulin involves the dephosphorylation of serine residues that are phosphorylated by gsk3 and dephosphorylated by the glycogen-associated form of protein phosphatase-l (pp1g).

SIGNOR-37301

P06493

Q9UKT4

1

phosphorylation

down-regulates quantity by destabilization

0.753

We find that both Emi1 phosphorylation by cyclin and Cdc2 and phosphorylation on a consensus site (DSGxxS) direct recruitment of betaTrCP and subsequent Emi1 ubiquitination and destruction.

SIGNOR-279143

O94759

P17252

0

phosphorylation

up-regulates activity

0.2

ROS production in endothelial cells or directly applying ROS induced PKC\u03b1 activation and phosphorylation of TRPM2 at Ser 39.|ROS production in endothelial cells or directly applying ROS induced PKCalpha activation and phosphorylation of TRPM2 at Ser 39.

SIGNOR-280082

P27361

Q02548

1

phosphorylation

down-regulates activity

0.247

In this study, we demonstrated that PAX5 was phosphorylated by ERK1/2 in vitro and in vivo at serines 189 and 283. This phosphorylation attenuated the transcriptional repression of BLIMP1 by PAX5.

SIGNOR-269086

Q96T51

P51813

0

phosphorylation

up-regulates activity

0.634

Etk interacts with RUFY1 through its SH3 and SH2 domains. RUFY1 is tyrosine-phosphorylated and appears to be a substrate of Etk. Phosphorylation of the two tyrosine residues, Tyr-281 and Tyr-292, located in the linker region of the two coiled-coil domains by Etk seems to be critical for RUFY1 targeting to the endosomes.

SIGNOR-262679

O00418

Q16539

0

phosphorylation

down-regulates activity

0.334

Inhibition of eEF2 kinase resulting from phosphorylation of Ser-396 by SAPK2a p38 was approx.25%.

SIGNOR-249707

Q15418

Q9HC62

1

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

P23677

Q9UQM7

0

phosphorylation

up-regulates

0.329

D-myo-inositol 1,4,5-trisphosphate 3-kinase a is activated by receptor activation through a calcium:calmodulin-dependent protein kinase ii phosphorylation mechanism. the phosphorylated residue was thr311.

SIGNOR-48387

Q9Y4L5

P00533

1

polyubiquitination

down-regulates quantity by destabilization

0.375

RNF126 and Rabring7 associate with the EGFR through a ubiquitin-binding zinc finger domain and both E3 ubiquitin ligases promote ubiquitylation of EGFR. In HeLa cells depleted of either RNF126 or Rabring7 the EGFR is retained in a late endocytic compartment and is inefficiently degraded.

SIGNOR-272104

Q07955

P21127

0

phosphorylation

up-regulates activity

0.283

In comparison, CLK1 expression leads to speckle dissolution and diffuse GFP-SRSF1 localization in the nucleus.|We showed that CLK1 phosphorylates SRSF1 at approximately 18 sites inducing a gel shift from 35 to about 38 kDa on SDS-PAGE (XREF_FIG, upper panel).

SIGNOR-279499

P11309

O95644

1

phosphorylation

up-regulates activity

0.643

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-276775

Q15942

P06493

0

phosphorylation

up-regulates activity

0.309

As predicted by our hypothesis, the Cdc2 dependent phosphorylation has been shown to allow the full-length zyxin to interact with h-warts and LATS1 (XREF_FIG A).|Phosphorylation of Zyxin by Cdc2 Regulates Binding to h-warts and LATS1.

SIGNOR-279498

P18848

Q9Y2Z4

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-269432

P24941

Q13118

1

phosphorylation

up-regulates quantity

0.329

In this study we have shown that CDK2 phosphorylates KLF10 at residue Ser 206 in vivo and in vitro .|In this study, we have shown that KLF10 protein has tightly controlled expression and that the expression level varies in a cell cycle dependent manner whereby CDK2 up-regulates activity the protein level of KLF10 through interference with the protein 's association with SIAH1.

SIGNOR-278394

P62826

Q9NRC8

0

deacetylation

down-regulates activity

0.2

N this study, we demonstrated that SIRT7 interacts with a small GTPase, Ras-related nuclear antigen (Ran), and deacetylates Ran at K37. |The nuclear export by CRM1 requires an interaction with the small GTPase Ras-related nuclear antigen (Ran), which cycles between GTP- and GDP-bound states. The binding of Ran GTP to CRM1 in the nucleus increases the affinity of CRM1 for cargo proteins [[18], [19], [20]]. Interestingly, Ran is a lysine-acetylated protein

SIGNOR-275849

Q06124

Q15116

1

dephosphorylation

down-regulates activity

0.659

Related to the latter notion, we recently showed that SHP2 dephosphorylates PD-1 to disassemble the PD-1:SHP2 complex ( xref ).

SIGNOR-277052

Q68DK7

Q16778

1

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-271977

Q8IVP5

Q96HS1

0

dephosphorylation

up-regulates activity

0.627

Here, we identify that the mitochondrially localized PGAM5 phosphatase interacts with and dephosphorylates FUNDC1 at serine 13 (Ser-13) upon hypoxia or carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP) treatment. Dephosphorylation of FUNDC1 catalyzed by PGAM5 enhances its interaction with LC3, which is abrogated following knockdown of PGAM5 or the introduction of a cell-permeable unphosphorylated peptide encompassing the Ser-13 and LIR of FUNDC1. We further observed that CK2 phosphorylates FUNDC1 to reverse the effect of PGAM5 in mitophagy activation.

SIGNOR-273654

Q99683

Q9H2G2

0

phosphorylation

up-regulates

0.253

Induction of apoptosis by the ste20-like kinase slk, a germinal center kinase that activates apoptosis signal-regulating kinase and p38

SIGNOR-142665

Q9UPN4

O00444

0

phosphorylation

up-regulates activity

0.534

We conclude that PLK4 phosphorylates CEP131 at Ser 78 to maintains centriolar satellite integrity.

SIGNOR-280075

Q15465

Q5VTY9

0

palmitoylation

up-regulates

0.683

Our molecular analysis of knockout mice deficient in skn, the murine homolog of the drosophila ski gene, which catalyzes hh palmitoylation, and gene-targeted mice producting a non palmitoylated form of shh indicates that hh palmitoylation is essential for its activity as well as the generation of a protein gradient in the developing embryos

SIGNOR-124118

P19525

Q9H3R0

1

phosphorylation

down-regulates quantity by destabilization

0.2

In the absence of Wnt3a, protein kinase R phosphorylated KDM4C at Ser918, inducing KDM4C ubiquitination and degradation.

SIGNOR-277497

Q96FF9

P06493

0

phosphorylation

down-regulates activity

0.711

Here we show that the mitotic kinases Aurora B and Cyclin-dependent kinase 1 (Cdk1) destabilize interactions between Sororin and the cohesin subunit precocious dissociation of sisters protein 5 (Pds5) by phosphorylating Sororin, leading to release of acetylated cohesin from chromosome arms and loss of cohesion.

SIGNOR-276118

P17252

Q9H3Q1

1

phosphorylation

down-regulates activity

0.2

Cdc42 effector protein-4 (CEP4) was recently identified by our laboratory to be a substrate of multiple PKC isoforms in non-transformed MCF-10A human breast cells. MS/MS analysis verified that Ser(18) and Ser(80) were directly phosphorylated by PKCα in vitro. Phosphorylation of CEP4 severely diminished its affinity for Cdc42 while promoting Rac activation and formation of filopodia (microspikes).

SIGNOR-263160

Q96JA1

Q15303

1

ubiquitination

down-regulates

0.608

We report upregulation of lrig1 transcript and protein upon egf stimulation, and physical association of the encoded protein with the four egfr orthologs of mammals. Upregulation of lrig1 is followed by enhanced ubiquitylation and degradation of egfr. The underlying mechanism involves recruitment of c-cbl, an e3 ubiquitin ligase that simultaneously ubiquitylates egfr and lrig1 and sorts them for degradation.

SIGNOR-139954

O00327

P35398

0

transcriptional regulation

up-regulates quantity by expression

0.689

Direct Regulation of the NPAS2 Promoter by RORα and REV-ERBα. it appears in the context of the NPAS2 promoter RORα functions as a transcriptional activator, but REV-ERBα may only function as an inhibitor of RORα activity by blocking binding.

SIGNOR-267982

P08195

Q5T0T0

0

polyubiquitination

down-regulates quantity by destabilization

0.2

Taken together, these findings demonstrate that MARCH8 directly ubiquitinates CD98, and this likely leads to its routing to late endosomes for degradation.

SIGNOR-272755

P38398

O96017

0

phosphorylation

up-regulates

0.787

In this study, we tested the hypothesis that the brca1-mediated regulation of recombination requires the chk2- and atm-dependent phosphorylation sites.

SIGNOR-120575

P68400

P78344

1

phosphorylation

up-regulates activity

0.226

DAP5(S902) is phosphorylated by CK2α. Phosphorylation of DAP5(S902) by CK2α is required for eIF2β binding.

SIGNOR-266384

P45984

Q9UIG0

1

phosphorylation

up-regulates

0.2

Wstf, a specific component of two chromatin remodeling complexes (swi/snf-type winac and iswi-type wich), was phosphorylated by the stimulation of mapk cascades in vitro and in vivo. Ser-158 residue in the wac (wstf/acf1/cbpq46) domain, located close to the n terminus of wstf, was identified as a major phosphorylation target

SIGNOR-188168

P40763

Q16827

0

dephosphorylation

down-regulates activity

0.376

In addition, this group found that PTPRO dephosphorylated STAT3 at Y705 and S727 then attenuated STAT3 signalling.

SIGNOR-277062

Q9HAU4

O95630

1

polyubiquitination

down-regulates quantity by destabilization

0.529

RNF11 recruits AMSH to Smurf2 E3 ligase. Smurf2 promotes ubiquitination of AMSH in the presence of wt RNF11. Previously, we have shown that RNF11 interacts with the HECT-type E3 ligases AIP4 and Smurf2. Here, we show that RNF11 binds to AMSH in mammalian cells and that this interaction is independent of the RNF11 RING-finger domain and the PY motif. Our results also demonstrate that AMSH is ubiquitinated by Smurf2 E3 ligase in the presence of RNF11 and that a consequent reduction in its steady-state level requires both RNF11 and Smurf2. RNF11 therefore recruits AMSH to Smurf2 for ubiquitination, leading to its degradation by the 26S proteasome.

SIGNOR-272951

Q969T9

P07947

0

phosphorylation

up-regulates activity

0.304

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

SIGNOR-273582

P10912

P17706

0

dephosphorylation

down-regulates activity

0.295

PTPH1 only bound Tyr534, whereas PTP1B and TC-PTP bound multiple phosphopeptides. Earlier work suggests that Tyr332, Tyr487, Tyr534, Tyr566, and Tyr627 are all phosphorylated after GH stimulation (21). Apart from Tyr627, all of these also appear good PTP substrates

SIGNOR-248394

Q92831

P0DPK5

1

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-269615

P09630

P04271

1

transcriptional regulation

up-regulates quantity by expression

0.2

HOXC6 and HOXC11 increase transcription of S100beta gene in BrdU-induced in vitro differentiation of GOTO neuroblastoma cells into Schwannian cells.

SIGNOR-261646

P46019

P22694

0

phosphorylation

down-regulates activity

0.325

Phosphorylation of the alpha and beta subunits by the 3',5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) also relieves inhibition of the gamma subunit and thereby activates the enzyme.

SIGNOR-267412

Q8IYT8

P19367

1

phosphorylation

up-regulates activity

0.2

Here, we demonstrate that, during deprivation of amino acid and growth factors, ULK1/2 directly phosphorylate key glycolytic enzymes including hexokinase (HK), phosphofructokinase 1 (PFK1), enolase 1 (ENO1), and the gluconeogenic enzyme fructose-1,6-bisphosphatase (FBP1).Phosphorylation of these enzymes leads to enhanced HK activity to sustain glucose uptake but reduced activity of FBP1 to block the gluconeogenic route and reduced activity of PFK1 and ENO1 to moderate drop of glucose-6-phosphate and to repartition more carbon flux to pentose phosphate pathway (PPP), maintaining cellular energy and redox homeostasis at cellular and organismal levels.Similar results were also obtained using ULK2 as the kinase (data not shown).

SIGNOR-274042

O60260

P42566

1

ubiquitination

up-regulates

0.2

Treatment of cells with egf stimulates parkin binding to both eps15 and the egfr and promotes parkin-mediated ubiquitination of eps15

SIGNOR-148218

P10070

P49841

0

phosphorylation

down-regulates quantity by destabilization

0.562

The degradation of Gli2 requires the phosphorylation of a cluster of numerous serine residues in its carboxyl terminus by protein kinase A and subsequently by casein kinase 1 and glycogen synthase kinase 3.

SIGNOR-249590

O14964

Q7Z6J0

0

ubiquitination

down-regulates quantity

0.246

Importantly, ubiquitination of Hrs mediated by POSH caused the reduction of Hrs level via the ubiquitin-proteasome pathway.

SIGNOR-278575

P04637

Q96Q15

0

phosphorylation

up-regulates

0.411

Hsmg-1 is a stress-activated kinase that phosphorylates p53 and hupf1 in vitrothe observation that hsmg-1 exhibits p53 (ser-15) kinase activity in vitro suggested that this pikk might be involved in genotoxic stress-induced p53 phosphorylation and stabilization in intact cells.

SIGNOR-125135

O15217

P0DMV9

0

relocalization

up-regulates activity

0.2

Model showing Ser189/Thr193 protein kinase dependent phosphorylation of GST A4‐4 has increased affinity for chaperone Hsp70 which activates mitochondrial competent import signals for GSTA4‐4. |Protein kinase A mediated phosphorylation of serine residues of CYPs increases the affinity of proteins for binding to cytoplasmic chaperones such as heat shock proteins (Hsp), Hsp70/Hsp90, resulting in increased mitochondrial translocation

SIGNOR-264800

P30304

P49137

0

phosphorylation

down-regulates

0.364

Mk2 was required for the degradation of cdc25a. Mk2 phosphorylates cdc25a in vitro. Phosphorylation of cdc25a in vivo has been shown to facilitate its ubiquitin-mediated proteolysis

SIGNOR-152996

Q14145

Q9NY33

0

cleavage

down-regulates quantity by destabilization

0.599

The influence of DPP3 on the Keap1-Nrf2/ARE signal pathway suggest a direct involvement of DPP3 in the oxidative stress response [8,14,31,53,99,100]. It was shown that DPP3 competes with Nrf2 through the ETGE motif to bind to Keap1 and consequently enhances the translocation of Nrf2 to the nucleus, thereby driving the expression of an array of genes encoding antioxidative enzymes [99]. More specifically, binding of DPP3 to Keap1 releases Nrf2, and thus, prevents its degradation through the 26S proteasome

SIGNOR-268464

Q9NS23

P11802

0

phosphorylation

down-regulates

0.409

This skp2-dependent destruction of rassf1a requires phosphorylation of the latter on serine-203 by cyclin d-cyclin-dependent kinase 4.

SIGNOR-159849