GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
P49137	Q00613	1	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
P24941	P10644	1	phosphorylation	up-regulates	0.343	In this context, we have identified rialpha as a novel substrate for the g(1)/s-cyclin-dependent kinase, cdk2/cyclin e, and found that rialpha is specifically phosphorylated at the serine residue.	SIGNOR-145577
Q9UQ52	P46531	1	relocalization	up-regulates	0.588	Here, we establish that nb-3, a member of the f3/contactin family, acts as a novel notch ligand to participate in oligodendrocyte generation. Nb-3 triggers nuclear translocation of the notch intracellular domain and promotes oligodendrogliogenesis from progenitor cells and differentiation of oligodendrocyte precursor cells via deltex1.	SIGNOR-124151
Q8IXL6	Q9BRK5	1	phosphorylation	up-regulates activity	0.2	Together, these results indicate that Fam20C kinase activity drives the sorting and secretion of the Cab45 dependent client LyzC.\|We show that Fam20C phosphorylates Cab45 on distinct residues and thereby decreases Cab45 retention in the TGN.	SIGNOR-279330
P98170	P42574	1	ubiquitination	down-regulates quantity by destabilization	0.939	Xiap promotes the degradation of active-form caspase-3, but not procaspase-3, in living cells. Both the association of XIAP with caspase-3 and the RING finger domain of XIAP were essential for ubiquitination. XIAP promotes the degradation of caspase-3, which enhances its anti-apoptotic effect.	SIGNOR-109243
P49815	P27361	0	phosphorylation	down-regulates activity	0.694	Here, we show that Erk may play a critical role in TSC progression through posttranslational inactivation of TSC2. Erk-dependent phosphorylation leads to TSC1-TSC2 dissociation and markedly impairs TSC2 ability to inhibit mTOR signaling, cell proliferation, and oncogenic transformation. \|Serine to alanine substitution at S664 or double S664A/S540A mutagenesis resulted in a marked reduction in TSC2 phosphorylation to a similar extent. In contrast, S540A substitution only moderately impaired TSC2 phosphorylation (Figure 3D), corroborating the notion that in vivo S664 is the most relevant residue for Erk-mediated phosphorylation.	SIGNOR-249457
Q9UQ13	P27361	0	phosphorylation	down-regulates quantity by destabilization	0.335	Here, we showed that SHOC2, a RAS activator, is a FBXW7 substrate. Growth stimuli trigger SHOC2 phosphorylation on Thr507 by the mitogen-activated protein kinase (MAPK) signal, which facilitates FBXW7 binding for ubiquitylation and degradation.	SIGNOR-277443
O14795	Q9UJD0	0	relocalization	up-regulates activity	0.266	N-terminal interactions of RIMs with RAB3 and MUNC13 regulate DCV fusion. Through N-terminal interactions, RIMs position MUNC13 and recruit DCVs via RAB3, which is located on the vesicle	SIGNOR-264384
P23443	P08151	1	phosphorylation	up-regulates	0.523	In this study, we found that an activated mtor/s6k1 pathway promotes gli1 transcriptional activity and oncogenic function through s6k1-mediated gli1 phosphorylation at ser84, which releases gli1 from its endogenous inhibitor, sufu.	SIGNOR-196756
P60484	Q99801	1	dephosphorylation	up-regulates quantity by stabilization	0.441	Loss of PTEN Accelerates NKX3.1 Degradation to Promote Prostate Cancer Progression.\|PTEN was also able to dephosphorylate NKX3.1 at threonine 179, a target of protein kinase C, but not threonine residues 89 and 93, targeted by casein kinase 2 .	SIGNOR-277026
P67870	P06493	0	phosphorylation	up-regulates	0.459	In cells, the casein kinase ii beta-subunit is phosphorylated at an autophosphorylation site and at a site (ser-209) that is maximally phosphorylated in mitotic cells. These studies provide strong biochemical evidence that p34cdc2 is the enzyme that phosphorylates ser-209 on the beta-subunit of ckii in mitotic cells.	SIGNOR-29462
O43318	P67775	0	dephosphorylation	down-regulates	0.329	Our results demonstrate that pp6 specifically down-regulates tak1 through dephosphorylation of thr-187 in the activation loop, which is likely important for suppressing inflammatory responses via tak1 signaling pathways.	SIGNOR-150369
Q9UIG0	P16104	1	phosphorylation	up-regulates	0.2	We show that wstf phosphorylates tyr 142 of h2a.x, and that wstf activity has an important role in regulating several events that are critical for the dna damage response	SIGNOR-182831
P31749	Q13363	1	phosphorylation	down-regulates quantity	0.483	Co-expression of Pc2 and Akt1 results in both phosphorylation and ubiquitylation of CtBP1, thereby targeting CtBP1 for degradation.\|CtBP1 phosphorylation by Akt1 appears to both decrease dimerization and induce ubiquitylation.	SIGNOR-278304
P41279	P36507	1	phosphorylation	up-regulates	0.436	Cot proteins were used in an in vitro kinase assay using mek as a substrate. Samples were analyzed by western blotting. As seen in the cascade activity assay only wild-type cot was active against mekregulation of cot is of great interest to the signaling field since the cot/mek/erk pathway potentially plays a role in the etiology of inflammatory autoimmune diseases.	SIGNOR-129694
Q09472	Q96EB6	0	deacetylation	down-regulates	0.835	Sirt1 induces deacetylation and repression of p300 itself (81). Mutational analysis demonstrated that sirt1 repression of p300 involves both lysine 1020 and lysine 1024	SIGNOR-182511
Q9NRM7	O95863	1	phosphorylation	up-regulates	0.528	Lats2 kinase potentiates snail1 activity by promoting nuclear retention upon phosphorylation. during tgf_-induced emt lats2 is activated and snail1 phosphorylated at t203.	SIGNOR-176647
P06850	P02533	1	transcriptional regulation	down-regulates quantity by repression	0.2	CRH stimulated the expression of cytokeratin 1 and involucrin, and inhibited cytokeratin 14 on both mRNA and protein levels.	SIGNOR-251899
P13569	Q8IWU2	0	phosphorylation	down-regulates activity	0.401	The present study discovered that in human airway epithelial cells CFTR endocytosis is regulated by the LMTK2-mediated phosphorylation of CFTR-Ser737 that decreases the cell surface density of CFTR Cl\u2212 channels and inhibits CFTR-mediated Cl\u2212 secretion.\|Together, the above results demonstrate that the LMTK2 phosphorylation of CFTR-Ser737 facilitates CFTR endocytosis and reduces the plasma membrane abundance of CFTR in human airway epithelial cells.	SIGNOR-278227
P50553	O94907	1	transcriptional regulation	down-regulates quantity by repression	0.306	We demonstrate that a critical factor in the set, ASCL1, activates Wnt signaling by repressing the negative regulator DKK1.	SIGNOR-245885
Q9UMS6	Q13418	0	phosphorylation	up-regulates activity	0.503	Fourth, ILK dependent phosphorylation of myopodin is found both in vivo and in vitro.\|The ILK dependent activation of myopodin provides a novel link between extracellular matrix-integrin-ILK signaling and myopodin tumor suppression.	SIGNOR-279622
P45984	Q13526	1	phosphorylation	up-regulates quantity by stabilization	0.2	Mechanistically, the JNK kinases directly bind to and phosphorylate PIN1 at Ser115, and this phosphorylation prevents PIN1 mono-ubiquitination at Lys117 and its proteasomal degradation.	SIGNOR-277563
Q9H9S0	Q9UJQ4	0	transcriptional regulation	up-regulates quantity by expression	0.792	We conclude that the Nanog enhancer activity is regulated by both Sall4 and Nanog.	SIGNOR-266079
Q13315	Q13362-1	1	phosphorylation	up-regulates activity	0.378	In the present study, we demonstrate that ataxia-telangiectasia mutated (ATM) directly phosphorylates and specifically regulates B56γ3, B56γ2 and B56δ, after DNA damage. We further show that phosphorylation of B56γ3 at Ser510 leads to an increase in B56γ3-PP2A complexes, and direction of PP2A phosphatase activity toward the substrate p53, activating its tumor-suppressive functions. we show that Ser510 phosphorylation significantly enhances the ability of B56γ3 to inhibit cell proliferation and anchorage-independent growth.	SIGNOR-276318
P48431	P31749	0	phosphorylation	up-regulates quantity by stabilization	0.532	In contrast, phosphorylation of Sox2 by AKT1 at T118 blocks K119me by Set7 and stabilizes Sox2.	SIGNOR-279003
Q8TD19	Q9HC98	1	phosphorylation	up-regulates activity	0.69	Nercc1/nek9 activates the nek6 and nek7 kinases. Nercc1 catalyzes the direct phosphorylation of prokaryotic recombinant nek6 at ser206 in vitro concomitant with 20-25-fold activation of nek6 activity.	SIGNOR-102996
P01266	P27695	0	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
P30291	Q9Y5B0	0	dephosphorylation	up-regulates activity	0.382	At mitosis exit, Fcp1 promoted inhibitory Cdk1 phosphorylation by dephosphorylating Wee1, and ubiquitin dependent cyclin B degradation by dephosphorylating Cdc20 and USP44.\|This lead us to hypothesize that, during prolonged mitosis in AMCDs treated cancer cells, progressive Fcp1 induced Wee1 reactivation might lead to progressive loss of Cdk1 activity that weakens the SAC to a point in which the mitotic state could not be sustained .	SIGNOR-277142
P17706	P40763	1	dephosphorylation	down-regulates	0.735	The nuclear isoform of protein-tyrosine phosphatase tc-ptp regulates interleukin-6-mediated signaling pathway through stat3 dephosphorylation.	SIGNOR-90818
P06493	Q12888	1	phosphorylation	down-regulates activity	0.599	Nuclear import of 53BP1 is required for proper localization of 53BP1 and maintenance of genome integrity. 53BP1 has a classical bipartite nuclear localization signal (NLS) of sequence 1666-GKRKLITSEEERSPAKRGRKS-1686. Ser1678 within the 53BP1 NLS can be phosphorylated by CDK1/cyclin B, and a phosphomimetic substitution of Ser1678 with aspartate has been shown to negatively regulate nuclear import of 53BP1.	SIGNOR-264412
Q9Y6W6	Q14653	1	dephosphorylation	down-regulates activity	0.2	The inactivation of IRF3 by MKP5 is dependent on MKP5 phosphatase activity or its binding to IRF3.\|This is confirmed since MKP5 phosphatasedeficient mutant is unable to dephosphorylate IRF3 and MKP5 mutant lacking IRF3 binding motifs fails to suppress IRF3 nuclear translocation upon virus infection.	SIGNOR-277146
P34925	Q9NZ42	0	cleavage	up-regulates	0.2	Ryk activity is modulated through cleavage of its icd by gamma-secretase	SIGNOR-182145
Q9BXM7	P61006	1	phosphorylation	down-regulates activity	0.271	For Rab8a, it was shown that serine 111 phosphorylation (pS111) is dependent on the protein kinase PINK1 and that mimicking the phosphorylation at S111 by a serine/glutamate substitution (S111E) impaired Rab8a activation by its cognate nucleotide exchange factor (GEF) Rabin8.	SIGNOR-260268
P06493	Q9GZM8	1	phosphorylation	up-regulates activity	0.66	In this case, only NudelS2 and NudelS5 were phosphorylated. Therefore, T219, S242, and T245 of Nudel were phosphorylation sites of Cdc2 in vitro. In contrast, Erk2 only phosphorylated T219 and T245. These two sites, with surrounding sequences such as PATP from residues 217 to 220 and PLTP from 243 to 246, respectively, are indeed typical MAPK sites	SIGNOR-274074
Q13153	Q15831	0	phosphorylation	down-regulates	0.247	Lkb1 suppresses p21-activated kinase-1 (pak1) by phosphorylation of thr109 in the p21-binding domain.	SIGNOR-164814
Q9UPX8	O14490	0	relocalization	up-regulates activity	0.827	SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3).	SIGNOR-264587
Q6P1J9	Q13882	0	phosphorylation	down-regulates activity	0.368	PTK6 impairs the coactivator function of parafibromin.\|To study the functional consequence of parafibromin phosphorylation by PTK6, we examined the effect of PTK6 inhibition on Wnt signal activation.	SIGNOR-279273
O43283	Q14258	1	phosphorylation	up-regulates quantity by stabilization	0.2	Mechanistically, MAP3K13 phosphorylates the E3 ubiquitin ligase TRIM25 at Ser12 to decrease its polyubiquitination and proteasomal degradation.	SIGNOR-277456
P42680	P51813	1	phosphorylation	up-regulates activity	0.332	Tec family protein tyrosine kinases (TFKs) play a central role in hematopoietic cellular signaling. Initial activation takes place through specific tyrosine phosphorylation situated in the activation loop.The major phosphorylation sites were identified as conserved tyrosines, for Itk Y180 and for Bmx Y215, both sites being homologous to the Y223 site in Btk	SIGNOR-246647
P62136	P15056	1	dephosphorylation	up-regulates activity	0.294	To address whether PP1\u03b1 activates B-Raf through these inhibitory sites, we made use of B-Raf protein mutants in which an individual inhibitory site, as well as all four sites (4A), were mutated to alanine.\|We confirmed that GST-B-Raf was phosphorylated by ERK2 in vitro xref , mainly on S151 and T753 (Fig.\u00a0 xref ), and found that PP1\u03b1 dephosphorylated B-Raf on both ERK phosphorylation sites (Fig.\u00a0 xref ).	SIGNOR-277160
O15530	Q16513	1	phosphorylation	up-regulates	0.705	It is shown that activation in vitro and in vivo involves the activation loop phosphorylation of prk1/2 by 3-phosphoinositide-dependent protein kinase-1 (pdk1) /pdk1 phosphorylates the prks at their conserved activation loop threonines (thr-774 and thr-816 for prk1 and prk2, respectively)	SIGNOR-76710
Q14940	P25098	0	phosphorylation	down-regulates activity	0.2	Simultaneous mutation of five Ser/Thr residues within 702-714 to Ala ((702)ST/AA(714)) abolished phosphorylation and binding of beta-arrestin2. In transfected cells, the CK2 catalytic alpha subunit formed a complex with NHE5 and decreased wild-type but not (702)ST/AA(714) NHE5 activity, further supporting a regulatory role for this kinase. The rate of internalization of (702)ST/AA(714) was also diminished and relatively insensitive to overexpression of beta-arrestin2.	SIGNOR-275503
Q9Y570	P62714	1	demethylation	down-regulates activity	0.716	Methylation of the carboxy-terminal Leu309 in a conserved TPDYFL309 motif of the C subunit has been shown to enhance the affinity of the PP2A core enzyme for some, but not all, regulatory subunits \|Demethylation and negative regulation of PP2A is mediated by a PP2A-specific methylesterase PME-1, which is conserved from yeast to humans.	SIGNOR-265750
P24941	Q8IZL8	1	phosphorylation	up-regulates	0.367	We identified ser(477) and ser(991) of pelp1 as cdk phosphorylation sites. we conclude that pelp1 is a novel substrate of interphase cdks and that its phosphorylation is important for the proper function of pelp1 in modulating hormone-driven cell cycle progression and also for optimal e2f transactivation function.	SIGNOR-167766
P31749	P24666	0	dephosphorylation	down-regulates activity	0.321	Reduction in the levels of both LMW-PTP isoforms in vitro and in vivo increased tyrosine phosphorylation of IR and AktSer473 and increased IRS-1- and IRS-2-associated PI3-K activities in both liver and fat.\|Activated PI3-K stimulates Akt (or protein kinase B) that in turn phosphorylates and inactivates glycogen synthase kinase-3	SIGNOR-248455
P05771	Q8IWA4	1	phosphorylation	down-regulates activity	0.2	Here we report that βIIPKC accumulates on the mitochondrial outer membrane and phosphorylates mitofusin 1 (Mfn1) at serine 86. Mfn1 phosphorylation results in partial loss of its GTPase activity and in a buildup of fragmented and dysfunctional mitochondria in heart failure.	SIGNOR-273826
Q13285	P28482	0	phosphorylation	up-regulates activity	0.463	Here we show that maximal SF-1-mediated transcription and interaction with general nuclear receptor cofactors depends on phosphorylation of a single serine residue (Ser-203) located in a major activation domain (AF-1) of the protein. Moreover, phosphorylation-dependent SF-1 activation is likely mediated by the mitogen-activated protein kinase (MAPK) signaling pathway.	SIGNOR-249431
P11908	P01106	0	transcriptional regulation	up-regulates quantity by expression	0.277	Analysis of in vivo C-MYC interactions with TS, IMPDH2 and PRPS2 genes confirmed that they are direct C-MYC targets. C-MYC depletion did not significantly affect levels of E2F1 protein reported to regulate expression of many S-phase specific genes, but resulted in the repression of several genes encoding enzymes rate-limiting for dNTP metabolism. These included thymidylate synthase (TS), inosine monophosphate dehydrogenase 2 (IMPDH2) and phosphoribosyl pyrophosphate synthetase 2 (PRPS2). C-MYC depletion also resulted in reduction in the amounts of deoxyribonucleoside triphosphates (dNTPs) and inhibition of proliferation.	SIGNOR-267376
P14672	P04637	0	transcriptional regulation	down-regulates quantity by repression	0.335	P53 regulates basal expression of AIF and SCO2 and facilitates oxidative phosphorylation. The expression of GLUT1, GLUT4, and HK2 is negatively regulated by p53, whereas TIGAR expression is induced by p53. The net result of p53-mediated regulation of these glycolytic enzymes is the suppression of glycolysis. In addition, p53 directly binds and inhibits G6PD activity and downregulates the pentose phosphate pathway.	SIGNOR-267465
Q68EM7	P63000	1	guanine nucleotide exchange factor	up-regulates activity	0.566	ARHGAP17 is a Rho GTPase-activating protein of Rac1	SIGNOR-272166
Q13490	O43353	1	polyubiquitination	up-regulates activity	0.652	CIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1-4).Together, our results demonstrate that depleting cIAP1/2 inhibits RIP1-4 mediated NF-kB activation without affecting RIP auto-phosphorylation.	SIGNOR-272712
Q92934	P27361	0	phosphorylation	down-regulates	0.483	Erk-1 map kinase prevents tnf-induced apoptosis through bad phosphorylation and inhibition of bax translocation in hela cells.	SIGNOR-188172
P26599	P17612	0	phosphorylation	down-regulates activity	0.309	PKA directly phosphorylates PTB on conserved Ser-16, and PKA activation in PC12 cells induces Ser-16 phosphorylation. PTB carrying a Ser-16 to alanine mutation accumulates normally in the nucleus. However, export of this mutant protein from the nucleus is greatly reduced in heterokaryon shuttling assays. Conversely, hyperphosphorylation of PTB by coexpression with the catalytic subunit of PKA results in the accumulation of PTB in the cytoplasm.	SIGNOR-263149
P12830	O14770	0	transcriptional regulation	up-regulates quantity by expression	0.2	We show that the Pbx1 and Meis2 homeodomain proteins interact with Klf4 and can be recruited to DNA elements comprising a Klf4 site or G C box, with adjacent Meis and Pbx sites. Meis2d and Pbx1a activate expression of p15(Ink4a) and E-cadherin, dependent on the Meis2d transcriptional activation domain. We suggest a model in which genes with Klf4 sites can be cooperatively activated by Meis2/Pbx1 and Klf4, dependent primarily on recruitment by Klf4.	SIGNOR-267242
Q8WY64	P01130	1	ubiquitination	down-regulates quantity by destabilization	0.723	The RING E3 ubiquitin ligase inducible degrader of the LDL receptor (IDOL, also known as MYLIP) promotes ubiquitylation and subsequent lysosomal degradation of the LDL receptor (LDLR), thus acting to limit uptake of lipoprotein-derived cholesterol into cells.	SIGNOR-271485
P49841	Q9Y4K4	0	phosphorylation	down-regulates	0.2	Gckr can phosphorylate an n-terminal recombinant fusion protein of gsk3_ and enhance the in vivo phosphorylation of gsk3_ on serine 9reduction of gckr expression inhibits wnt3a-induced phosphorylation of gsk3_ at serine 9 and decreases the accumulation of cytosolic _-catenin.	SIGNOR-148908
O95140	P45983	0	phosphorylation	down-regulates quantity	0.428	We demonstrate that a critical component of the mitochondrial fusion apparatus, the mitofusin Mfn2, is a target for phosphorylation in response to a variety of cellular stresses. We provide direct evidence that JNK mediates this phosphorylation.	SIGNOR-274138
P00519	Q70E73	1	phosphorylation	up-regulates activity	0.284	Here we show that phosphorylation of Lpd by c-Abl increases its interaction with Ena/VASP proteins. This analysis revealed that, in vitro, four Lpd peptides harboring tyrosines (Y426, Y456, Y513, Y1226) are highly phosphorylated, and eight additional peptides are phosphorylated to a lesser extent (Figure 1C).	SIGNOR-262606
P16220	Q16566	0	phosphorylation	up-regulates activity	0.708	Pka, ca2+-calmodulin-dependent kinase iv (camkiv), msk, p70s6k and rsk phosphorylate creb. All these kinases target CREB on S133 to activate CREB.	SIGNOR-102722
O95297	Q06124	0	dephosphorylation	down-regulates	0.522	In vitro, tyrosine-phosphorylated pzr was efficiently dephosphorylated by the full-length form of shp-2 but not by its sh2 domain-truncated form. The coexisting binding and dephosphorylation of pzr by shp-2 may function to terminate signal transduction initiated by pzr and shp-2 and to set a threshold for the signal transduction to be initiated.	SIGNOR-75220
Q9UQM7	Q06210	1	phosphorylation	up-regulates	0.2	Amp-activated protein kinase and calcium/calmodulin-dependent kinase ii were identified to phosphorylate specifically ser243 in vitro. Phosphorylation by these two kinases results in an increase of enzymatic activity by 1.4-fold. These findings suggest for the first time that hgfat1 may be regulated by kinases other than pka.	SIGNOR-158486
P62826	O96013	0	phosphorylation	up-regulates	0.308	We show that ran is a substrate for p21-activated kinase 4 (pak4) and that its phosphorylation on serine-135 increases during mitosis.Altogether, our findings strongly suggest that pak4-mediated phosphorylation of gdp- or gtp-bound ran modulates the assembly of complexes that are required at specific subcellular localizations for ran to carry out its functions during mitotic progression.	SIGNOR-167667
Q02078	P35580	1	transcriptional regulation	up-regulates quantity by expression	0.317	Myocyte enhancer factor-2 and serum response factor binding elements regulate fast Myosin heavy chain transcription in vivo. We show that the upstream promoter region of the gene most abundantly expressed in mouse skeletal muscles, IIb MyHC, retains binding activity and transcriptional activation for three positive transcription factors, the serum response factor, Oct-1, and myocyte enhancer factor-2, whereas the other two genes (IIa and IId/x) have nucleotide substitutions in these sites that reduce binding and transcriptional activation	SIGNOR-238763
P04004	P17252	0	phosphorylation	up-regulates quantity by stabilization	0.318	Phosphorylation of vitronectin on Ser362 by protein kinase C attenuates its cleavage by plasmin.	SIGNOR-248962
P31260	Q15910	0	transcriptional regulation	down-regulates quantity by repression	0.438	These data support the proposed regulatory impact of particular PRC2-proteins in expression of HOXA9 and HOXA10 in NK/T-cells. In mammalian cells knockdown of PRC2 components EZH2 or PHF1 led to upregulated HOXA gene expression.	SIGNOR-260070
O75688	Q9UHD2	1	dephosphorylation	down-regulates activity	0.352	PPM1B dephosphorylates TBK1 in vivo and in vitro.\|These results demonstrate that PPM1B inhibits TBK1 mediated antiviral signaling by directly dephosphorylating TBK1 at Ser172.	SIGNOR-276985
Q9UBE8	P46937	1	phosphorylation	up-regulates activity	0.2	Here, we report that osmotic stress stimulates transient YAP nuclear localization and increases YAP activity even when YAP Ser127 is phosphorylated. Osmotic stress acts via the NLK kinase to induce YAP Ser128 phosphorylation. Phosphorylation of YAP at Ser128 interferes with its ability to bind to 14-3-3, resulting in YAP nuclear accumulation and induction of downstream target gene expression.	SIGNOR-273909
P06748	P24941	0	phosphorylation	down-regulates activity	0.561	Both subtypes of B23 proteins were phosphorylated during mitosis by cyclin B/cdc2. The RNA binding activity of B23.1 was repressed through cyclin B/cdc2-mediated phosphorylation at specific sites in B23. Thus, the RNA binding activity of B23.1 is stringently modulated by its phosphorylation and subtype association.	SIGNOR-89609
Q05655	P61978	1	phosphorylation	down-regulates	0.344	Ser302 is a major k protein site phosphorylated by pkcdelta in vitrothe ability of pkc_ to inducibly bind and phosphorylate k protein may serve not only to alter the activity of k protein itself, but k protein may also provide an avenue for pkc_ to engage in a cross-talk with other k protein molecular partners in response to specific changes in the extracellular environment	SIGNOR-67515
P11387	P38398	0	ubiquitination	down-regulates quantity by destabilization	0.463	Here, we show that the Ku70/Ku80 heterodimer binds with topoI, and that the DNA-dependent protein kinase (DNA-PKcs) phosphorylates topoI on serine 10 (topoI-pS10), which is subsequently ubiquitinated by BRCA1. Taken together, we conclude that BRCA1 is the E3 ligase for topoI, and the rate of topoI proteasomal degradation determines CPT response.	SIGNOR-277353
Q14814	P12882	1	transcriptional regulation	up-regulates quantity by expression	0.34	Myocyte enhancer factor-2 and serum response factor binding elements regulate fast Myosin heavy chain transcription in vivo. We show that the upstream promoter region of the gene most abundantly expressed in mouse skeletal muscles, IIb MyHC, retains binding activity and transcriptional activation for three positive transcription factors, the serum response factor, Oct-1, and myocyte enhancer factor-2, whereas the other two genes (IIa and IId/x) have nucleotide substitutions in these sites that reduce binding and transcriptional activation	SIGNOR-238751
P62805	P25440	1	relocalization	up-regulates activity	0.2	Thus, the TIP60 HAT complex is recruited to MYC-target genes and, probably with other other HATs, contributes to histone acetylation in response to mitogenic signals.	SIGNOR-262062
Q68DV7	Q14332	1	relocalization	up-regulates	0.308	Frizzled receptors are regu__lated by cycles of ubiquitylation and deubiquitylation61 (see above), and znrf3 and rnf43 act as frizzled ubiquitin ligases, removing frizzled and possibly lrp6 from the plasma membrane	SIGNOR-199585
Q92974	P27361	0	phosphorylation	up-regulates	0.29	Activates rhoa and as a result regulates actin assembly.	SIGNOR-160420
Q9NZQ7	P49840	0	phosphorylation	down-regulates quantity by destabilization	0.2	We find EGFR inhibitors promote PD-L1 ubiquitination and proteasomal degradation following GSK3α-mediated phosphorylation of Ser279/Ser283. We identify ARIH1 as the E3 ubiquitin ligase responsible for targeting PD-L1 to degradation.	SIGNOR-277552
Q2PPJ7	P31751	0	phosphorylation	down-regulates activity	0.453	RGC2 is an endogenous substrate for Akt2 downstream of PI 3-kinase	SIGNOR-269799
P11362	Q14247	1	phosphorylation	down-regulates	0.313	Cortactin, which is an actin-binding protein that also plays a role in actin cytoskeleton dynamics (45), was phosphorylated on tyr-446 in our assay (by fgfr1).Phosphorylation of these residues attenuates the f-actin cross-linking activity	SIGNOR-98618
Q13627	P04637	1	phosphorylation	up-regulates	0.417	Dyrk1a phosphorylates p53 and inhibits proliferation of embryonic neuronal cells. we found that dyrk1a phosphorylates p53 at ser-15 in vitro and in immortalized rat embryonic hippocampal progenitor h19-7 cells. In addition, dyrk1a-induced p53 phosphorylation at ser-15 led to a robust induction of p53 target genes	SIGNOR-167407
P51812	P12931	0	phosphorylation	up-regulates	0.355	Together, our findings suggest that src-dependent phosphorylation at tyr-529 facilitates inactive erk binding to rsk2, which might be a general requirement for rsk2 activation by egf through the mek/erk pathway.	SIGNOR-160052
P17612	Q9NRM7	1	phosphorylation	up-regulates	0.2	Here, we show that cyclic amp (camp)-dependent protein kinase (pka) phosphorylates lats and thereby enhances its activity sufficiently to phosphorylate yap on ser381.	SIGNOR-236994
Q9Y6R4	P52564	1	phosphorylation	up-regulates activity	0.657	When truncated mapkkk4 (deltamapkkk4) was overexpressed in hek293 cells, it was constitutively activeco-expressed map kinase kinase (mkk)-1, mkk-4, mkk-3 and mkk-6 were activated in vivo by deltamapkkk4. All of the above mkks purified from escherichia coli were phosphorylated and activated by deltamapkkk4 immunoprecipitates in vitro.	SIGNOR-62372
P52630	P49841	0	phosphorylation	down-regulates quantity by destabilization	0.289	GSK3α/β are critical kinases to regulate STAT2 protein stability mediated by FBXW7.The 4-point mutant (STAT2-4A) of STAT2 at S381A/T385A/E389A/S393A inhibited GSK3α/β-mediated STAT2 phosphorylation.	SIGNOR-276764
Q9H6Z4	Q15796	1	relocalization	down-regulates activity	0.436	RanBP3 directly recognizes dephosphorylated Smad2/3, which results from the activity of nuclear Smad phosphatases, and mediates nuclear export of Smad2/3 in a Ran-dependent manner.	SIGNOR-217634
P17612	Q92934	1	phosphorylation	down-regulates	0.542	Ser-155 is the major phosphoacceptor site for pka on bad, but that pka also phosphorylates ser-112 and ser-136. Phosphorylated bad appears to be the inactive moiety. These results implicate pkac as the candidate kinase for s112 phosphorylation in vivo.	SIGNOR-67387
Q06787	P78352	1	post transcriptional regulation	up-regulates quantity	0.473	These results point toward a novel mechanism by which FUS targets neuronal mRNA and given that these PSD-95 and Shank1 3'-UTR G quadruplex structures are also targeted by the fragile X mental retardation protein (FMRP), they raise the possibility that FUS and FMRP might work together to regulate the translation of these neuronal mRNA targets.	SIGNOR-262108
P19174	Q08881	0	phosphorylation	up-regulates	0.637	In t cells, the predominant tec kinase is itk, which functions downstream of the t-cell receptor to regulate phospholipase c-gamma.	SIGNOR-165803
P12931	O95319	1	phosphorylation	up-regulates activity	0.321	Site-directed mutagenesis of putative tyrosine phosphorylation sites in CUGBP2 identified tyrosine 39 as a c-Src target, and a CUGBP2 with a mutated tyrosine 39 displayed an attenuated ability to bind COX-2 mRNA.	SIGNOR-263195
P31751	O43524	1	phosphorylation	down-regulates activity	0.751	Akt-dependent phosphorylation of foxo3a (thr32, ser253, and ser315 for human foxo3) enhances foxo3a/14-3-3 Interaction and promotes foxo3a nuclear export to the cytoplasm, resulting in the repression of foxo3a transcriptional function akt phosphorylates members of the foxo factors (forkhead family of transcription factors), leading to binding of 14-3-3 proteins and cytoplasmic localisation. In particular, akt phosphorylates foxo1 on thr24, ser256 and ser319. Foxo 3alfa and foxo4 are phosphorylated on equivalent sites.	SIGNOR-236671
P49116	Q13131	0	phosphorylation	down-regulates	0.2	Tr4 transactivation is inhibited via phosphorylation bymetformin-induced amp-activated protein kinase (ampk) at the amino acid serine 351, which results in the suppression of scd1 gene expression	SIGNOR-173118
Q16665	P11309	0	phosphorylation	up-regulates quantity by stabilization	0.2	PIM1 kinase directly phosphorylates HIF-1α at threonine 455, a previously uncharacterized site within its oxygen-dependent degradation domain. This phosphorylation event disrupts the ability of prolyl hydroxylases to bind and hydroxylate HIF-1α, interrupting its canonical degradation pathway and promoting constitutive transcription of HIF-1 target genes.	SIGNOR-277311
P84243	O75151	0	demethylation	up-regulates activity	0.2	PHF2, a jmjC demethylase, is enzymatically inactive by itself, but becomes an active H3K9Me2 demethylase through PKA-mediated phosphorylation. This modification leads to targeting of the PHF2–ARID5B complex to its target promoters, where it removes the repressive H3K9Me2 mark.	SIGNOR-264518
Q15118	P05106	1	phosphorylation	down-regulates activity	0.306	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-250264
P52566	Q8TEB7	0	polyubiquitination	up-regulates quantity by stabilization	0.2	We found that RhoGDIα and RhoGDIβ are ubiquitin E3 substrates of GRAIL. GRAIL uses nonlysine 48-ubiquitin linkage in polyubiquitinating RhoGDI. GRAIL was subsequently demonstrated to bind and ubiquitinate RhoGDI, although GRAIL-mediated ubiquitination of RhoGDI did not result in proteosomal degradation. Our data suggest that ubiquitination of RhoGDI by GRAIL does not result in proteolytic degradation. In fact, GRAIL activity appeared to increase RhoGDI stability.	SIGNOR-271621
O14733	P35568	1	phosphorylation	down-regulates activity	0.369	Tyrosine phosphorylation of IRS-1 initiates insulin signaling, whereas serine/threonine phosphorylation alters the ability of IRS-1 to transduce the insulin signalInsulin increased the phosphorylation of Ser312, Ser616, Ser636, Ser892, Ser1101, and Ser1223 Ser312 can be phosphorylated by kinases, such as c-jun NH2-terminal kinase and inhibitor of _B kinase	SIGNOR-217920
P31947	P45984	0	phosphorylation	down-regulates	0.2	Jnk phosphorylates 14-3-3zeta_ at ser-184 and 14-3-3sigma_ at ser-189	SIGNOR-124027
P00519	P46937	1	phosphorylation	up-regulates	0.718	In this study, we show that c-abl directly phosphorylates yap1 at position y357 in response to dna damage. Tyrosine-phosphorylated yap1 is a more stable protein that displays higher affinity to p73 and selectively coactivates p73 proapoptotic target genes.	SIGNOR-160860
Q8WZ42	Q5VST9	1	relocalization	up-regulates quantity	0.58	Ankyrin-B is targeted to the M-line via its interaction with the C-terminal domain of the large sarcomeric protein obscurin. Obscurin is targeted to the M-line via its N-terminal interactions with myomesin and titin. This population of ankyrin-B recruits B56α, a regulatory subunit of protein phosphatase 2A, to the M-line where the phosphatase may regulate the phosphorylation status of contractile and signalling proteins.	SIGNOR-266728
P27361	Q12913	0	dephosphorylation	down-regulates activity	0.459	Tumor suppressor density-enhanced phosphatase-1 (DEP-1) inhibits the RAS pathway by direct dephosphorylation of ERK1/2 kinases\|Pulldown and in vitro dephosphorylation assays confirmed our prediction and demonstrated an overall specificity of DEP-1 in targeting the phosphorylated tyrosine 204 of ERK1/2.	SIGNOR-248707
P68871	P15289	0	acetylation	up-regulates activity	0.2	ASA acetylates hemoglobin. Purified acetylated hemoglobin had a slightly increased oxygen affinity and decreased heme-heme interaction.	SIGNOR-251772
Q9BXM7	P62987	1	phosphorylation	up-regulates	0.385	Here we report that ubiquitin is the genuine substrate of PINK1. PINK1 phosphorylated ubiquitin at Ser 65 both in vitro and in cells, and a Ser 65 phosphopeptide derived from endogenous ubiquitin was only detected in cells in the presence of PINK1 and following a decrease in mitochondrial membrane potential.	SIGNOR-270342

P49137

Q00613

1

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

P24941

P10644

1

phosphorylation

up-regulates

0.343

In this context, we have identified rialpha as a novel substrate for the g(1)/s-cyclin-dependent kinase, cdk2/cyclin e, and found that rialpha is specifically phosphorylated at the serine residue.

SIGNOR-145577

Q9UQ52

P46531

1

relocalization

up-regulates

0.588

Here, we establish that nb-3, a member of the f3/contactin family, acts as a novel notch ligand to participate in oligodendrocyte generation. Nb-3 triggers nuclear translocation of the notch intracellular domain and promotes oligodendrogliogenesis from progenitor cells and differentiation of oligodendrocyte precursor cells via deltex1.

SIGNOR-124151

Q8IXL6

Q9BRK5

1

phosphorylation

up-regulates activity

0.2

Together, these results indicate that Fam20C kinase activity drives the sorting and secretion of the Cab45 dependent client LyzC.|We show that Fam20C phosphorylates Cab45 on distinct residues and thereby decreases Cab45 retention in the TGN.

SIGNOR-279330

P98170

P42574

1

ubiquitination

down-regulates quantity by destabilization

0.939

Xiap promotes the degradation of active-form caspase-3, but not procaspase-3, in living cells. Both the association of XIAP with caspase-3 and the RING finger domain of XIAP were essential for ubiquitination. XIAP promotes the degradation of caspase-3, which enhances its anti-apoptotic effect.

SIGNOR-109243

P49815

P27361

0

phosphorylation

down-regulates activity

0.694

Here, we show that Erk may play a critical role in TSC progression through posttranslational inactivation of TSC2. Erk-dependent phosphorylation leads to TSC1-TSC2 dissociation and markedly impairs TSC2 ability to inhibit mTOR signaling, cell proliferation, and oncogenic transformation. |Serine to alanine substitution at S664 or double S664A/S540A mutagenesis resulted in a marked reduction in TSC2 phosphorylation to a similar extent. In contrast, S540A substitution only moderately impaired TSC2 phosphorylation (Figure 3D), corroborating the notion that in vivo S664 is the most relevant residue for Erk-mediated phosphorylation.

SIGNOR-249457

Q9UQ13

P27361

0

phosphorylation

down-regulates quantity by destabilization

0.335

Here, we showed that SHOC2, a RAS activator, is a FBXW7 substrate. Growth stimuli trigger SHOC2 phosphorylation on Thr507 by the mitogen-activated protein kinase (MAPK) signal, which facilitates FBXW7 binding for ubiquitylation and degradation.

SIGNOR-277443

O14795

Q9UJD0

0

relocalization

up-regulates activity

0.266

N-terminal interactions of RIMs with RAB3 and MUNC13 regulate DCV fusion. Through N-terminal interactions, RIMs position MUNC13 and recruit DCVs via RAB3, which is located on the vesicle

SIGNOR-264384

P23443

P08151

1

phosphorylation

up-regulates

0.523

In this study, we found that an activated mtor/s6k1 pathway promotes gli1 transcriptional activity and oncogenic function through s6k1-mediated gli1 phosphorylation at ser84, which releases gli1 from its endogenous inhibitor, sufu.

SIGNOR-196756

P60484

Q99801

1

dephosphorylation

up-regulates quantity by stabilization

0.441

Loss of PTEN Accelerates NKX3.1 Degradation to Promote Prostate Cancer Progression.|PTEN was also able to dephosphorylate NKX3.1 at threonine 179, a target of protein kinase C, but not threonine residues 89 and 93, targeted by casein kinase 2 .

SIGNOR-277026

P67870

P06493

0

phosphorylation

up-regulates

0.459

In cells, the casein kinase ii beta-subunit is phosphorylated at an autophosphorylation site and at a site (ser-209) that is maximally phosphorylated in mitotic cells. These studies provide strong biochemical evidence that p34cdc2 is the enzyme that phosphorylates ser-209 on the beta-subunit of ckii in mitotic cells.

SIGNOR-29462

O43318

P67775

0

dephosphorylation

down-regulates

0.329

Our results demonstrate that pp6 specifically down-regulates tak1 through dephosphorylation of thr-187 in the activation loop, which is likely important for suppressing inflammatory responses via tak1 signaling pathways.

SIGNOR-150369

Q9UIG0

P16104

1

phosphorylation

up-regulates

0.2

We show that wstf phosphorylates tyr 142 of h2a.x, and that wstf activity has an important role in regulating several events that are critical for the dna damage response

SIGNOR-182831

P31749

Q13363

1

phosphorylation

down-regulates quantity

0.483

Co-expression of Pc2 and Akt1 results in both phosphorylation and ubiquitylation of CtBP1, thereby targeting CtBP1 for degradation.|CtBP1 phosphorylation by Akt1 appears to both decrease dimerization and induce ubiquitylation.

SIGNOR-278304

P41279

P36507

1

phosphorylation

up-regulates

0.436

Cot proteins were used in an in vitro kinase assay using mek as a substrate. Samples were analyzed by western blotting. As seen in the cascade activity assay only wild-type cot was active against mekregulation of cot is of great interest to the signaling field since the cot/mek/erk pathway potentially plays a role in the etiology of inflammatory autoimmune diseases.

SIGNOR-129694

Q09472

Q96EB6

0

deacetylation

down-regulates

0.835

Sirt1 induces deacetylation and repression of p300 itself (81). Mutational analysis demonstrated that sirt1 repression of p300 involves both lysine 1020 and lysine 1024

SIGNOR-182511

Q9NRM7

O95863

1

phosphorylation

up-regulates

0.528

Lats2 kinase potentiates snail1 activity by promoting nuclear retention upon phosphorylation. during tgf_-induced emt lats2 is activated and snail1 phosphorylated at t203.

SIGNOR-176647

P06850

P02533

1

transcriptional regulation

down-regulates quantity by repression

0.2

CRH stimulated the expression of cytokeratin 1 and involucrin, and inhibited cytokeratin 14 on both mRNA and protein levels.

SIGNOR-251899

P13569

Q8IWU2

0

phosphorylation

down-regulates activity

0.401

The present study discovered that in human airway epithelial cells CFTR endocytosis is regulated by the LMTK2-mediated phosphorylation of CFTR-Ser737 that decreases the cell surface density of CFTR Cl\u2212 channels and inhibits CFTR-mediated Cl\u2212 secretion.|Together, the above results demonstrate that the LMTK2 phosphorylation of CFTR-Ser737 facilitates CFTR endocytosis and reduces the plasma membrane abundance of CFTR in human airway epithelial cells.

SIGNOR-278227

P50553

O94907

1

transcriptional regulation

down-regulates quantity by repression

0.306

We demonstrate that a critical factor in the set, ASCL1, activates Wnt signaling by repressing the negative regulator DKK1.

SIGNOR-245885

Q9UMS6

Q13418

0

phosphorylation

up-regulates activity

0.503

Fourth, ILK dependent phosphorylation of myopodin is found both in vivo and in vitro.|The ILK dependent activation of myopodin provides a novel link between extracellular matrix-integrin-ILK signaling and myopodin tumor suppression.

SIGNOR-279622

P45984

Q13526

1

phosphorylation

up-regulates quantity by stabilization

0.2

Mechanistically, the JNK kinases directly bind to and phosphorylate PIN1 at Ser115, and this phosphorylation prevents PIN1 mono-ubiquitination at Lys117 and its proteasomal degradation.

SIGNOR-277563

Q9H9S0

Q9UJQ4

0

transcriptional regulation

up-regulates quantity by expression

0.792

We conclude that the Nanog enhancer activity is regulated by both Sall4 and Nanog.

SIGNOR-266079

Q13315

Q13362-1

1

phosphorylation

up-regulates activity

0.378

In the present study, we demonstrate that ataxia-telangiectasia mutated (ATM) directly phosphorylates and specifically regulates B56γ3, B56γ2 and B56δ, after DNA damage. We further show that phosphorylation of B56γ3 at Ser510 leads to an increase in B56γ3-PP2A complexes, and direction of PP2A phosphatase activity toward the substrate p53, activating its tumor-suppressive functions. we show that Ser510 phosphorylation significantly enhances the ability of B56γ3 to inhibit cell proliferation and anchorage-independent growth.

SIGNOR-276318

P48431

P31749

0

phosphorylation

up-regulates quantity by stabilization

0.532

In contrast, phosphorylation of Sox2 by AKT1 at T118 blocks K119me by Set7 and stabilizes Sox2.

SIGNOR-279003

Q8TD19

Q9HC98

1

phosphorylation

up-regulates activity

0.69

Nercc1/nek9 activates the nek6 and nek7 kinases. Nercc1 catalyzes the direct phosphorylation of prokaryotic recombinant nek6 at ser206 in vitro concomitant with 20-25-fold activation of nek6 activity.

SIGNOR-102996

P01266

P27695

0

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

P30291

Q9Y5B0

0

dephosphorylation

up-regulates activity

0.382

At mitosis exit, Fcp1 promoted inhibitory Cdk1 phosphorylation by dephosphorylating Wee1, and ubiquitin dependent cyclin B degradation by dephosphorylating Cdc20 and USP44.|This lead us to hypothesize that, during prolonged mitosis in AMCDs treated cancer cells, progressive Fcp1 induced Wee1 reactivation might lead to progressive loss of Cdk1 activity that weakens the SAC to a point in which the mitotic state could not be sustained .

SIGNOR-277142

P17706

P40763

1

dephosphorylation

down-regulates

0.735

The nuclear isoform of protein-tyrosine phosphatase tc-ptp regulates interleukin-6-mediated signaling pathway through stat3 dephosphorylation.

SIGNOR-90818

P06493

Q12888

1

phosphorylation

down-regulates activity

0.599

Nuclear import of 53BP1 is required for proper localization of 53BP1 and maintenance of genome integrity. 53BP1 has a classical bipartite nuclear localization signal (NLS) of sequence 1666-GKRKLITSEEERSPAKRGRKS-1686. Ser1678 within the 53BP1 NLS can be phosphorylated by CDK1/cyclin B, and a phosphomimetic substitution of Ser1678 with aspartate has been shown to negatively regulate nuclear import of 53BP1.

SIGNOR-264412

Q9Y6W6

Q14653

1

dephosphorylation

down-regulates activity

0.2

The inactivation of IRF3 by MKP5 is dependent on MKP5 phosphatase activity or its binding to IRF3.|This is confirmed since MKP5 phosphatasedeficient mutant is unable to dephosphorylate IRF3 and MKP5 mutant lacking IRF3 binding motifs fails to suppress IRF3 nuclear translocation upon virus infection.

SIGNOR-277146

P34925

Q9NZ42

0

cleavage

up-regulates

0.2

Ryk activity is modulated through cleavage of its icd by gamma-secretase

SIGNOR-182145

Q9BXM7

P61006

1

phosphorylation

down-regulates activity

0.271

For Rab8a, it was shown that serine 111 phosphorylation (pS111) is dependent on the protein kinase PINK1 and that mimicking the phosphorylation at S111 by a serine/glutamate substitution (S111E) impaired Rab8a activation by its cognate nucleotide exchange factor (GEF) Rabin8.

SIGNOR-260268

P06493

Q9GZM8

1

phosphorylation

up-regulates activity

0.66

In this case, only NudelS2 and NudelS5 were phosphorylated. Therefore, T219, S242, and T245 of Nudel were phosphorylation sites of Cdc2 in vitro. In contrast, Erk2 only phosphorylated T219 and T245. These two sites, with surrounding sequences such as PATP from residues 217 to 220 and PLTP from 243 to 246, respectively, are indeed typical MAPK sites

SIGNOR-274074

Q13153

Q15831

0

phosphorylation

down-regulates

0.247

Lkb1 suppresses p21-activated kinase-1 (pak1) by phosphorylation of thr109 in the p21-binding domain.

SIGNOR-164814

Q9UPX8

O14490

0

relocalization

up-regulates activity

0.827

SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3).

SIGNOR-264587

Q6P1J9

Q13882

0

phosphorylation

down-regulates activity

0.368

PTK6 impairs the coactivator function of parafibromin.|To study the functional consequence of parafibromin phosphorylation by PTK6, we examined the effect of PTK6 inhibition on Wnt signal activation.

SIGNOR-279273

O43283

Q14258

1

phosphorylation

up-regulates quantity by stabilization

0.2

Mechanistically, MAP3K13 phosphorylates the E3 ubiquitin ligase TRIM25 at Ser12 to decrease its polyubiquitination and proteasomal degradation.

SIGNOR-277456

P42680

P51813

1

phosphorylation

up-regulates activity

0.332

Tec family protein tyrosine kinases (TFKs) play a central role in hematopoietic cellular signaling. Initial activation takes place through specific tyrosine phosphorylation situated in the activation loop.The major phosphorylation sites were identified as conserved tyrosines, for Itk Y180 and for Bmx Y215, both sites being homologous to the Y223 site in Btk

SIGNOR-246647

P62136

P15056

1

dephosphorylation

up-regulates activity

0.294

To address whether PP1\u03b1 activates B-Raf through these inhibitory sites, we made use of B-Raf protein mutants in which an individual inhibitory site, as well as all four sites (4A), were mutated to alanine.|We confirmed that GST-B-Raf was phosphorylated by ERK2 in vitro xref , mainly on S151 and T753 (Fig.\u00a0 xref ), and found that PP1\u03b1 dephosphorylated B-Raf on both ERK phosphorylation sites (Fig.\u00a0 xref ).

SIGNOR-277160

O15530

Q16513

1

phosphorylation

up-regulates

0.705

It is shown that activation in vitro and in vivo involves the activation loop phosphorylation of prk1/2 by 3-phosphoinositide-dependent protein kinase-1 (pdk1) /pdk1 phosphorylates the prks at their conserved activation loop threonines (thr-774 and thr-816 for prk1 and prk2, respectively)

SIGNOR-76710

Q14940

P25098

0

phosphorylation

down-regulates activity

0.2

Simultaneous mutation of five Ser/Thr residues within 702-714 to Ala ((702)ST/AA(714)) abolished phosphorylation and binding of beta-arrestin2. In transfected cells, the CK2 catalytic alpha subunit formed a complex with NHE5 and decreased wild-type but not (702)ST/AA(714) NHE5 activity, further supporting a regulatory role for this kinase. The rate of internalization of (702)ST/AA(714) was also diminished and relatively insensitive to overexpression of beta-arrestin2.

SIGNOR-275503

Q9Y570

P62714

1

demethylation

down-regulates activity

0.716

Methylation of the carboxy-terminal Leu309 in a conserved TPDYFL309 motif of the C subunit has been shown to enhance the affinity of the PP2A core enzyme for some, but not all, regulatory subunits |Demethylation and negative regulation of PP2A is mediated by a PP2A-specific methylesterase PME-1, which is conserved from yeast to humans.

SIGNOR-265750

P24941

Q8IZL8

1

phosphorylation

up-regulates

0.367

We identified ser(477) and ser(991) of pelp1 as cdk phosphorylation sites. we conclude that pelp1 is a novel substrate of interphase cdks and that its phosphorylation is important for the proper function of pelp1 in modulating hormone-driven cell cycle progression and also for optimal e2f transactivation function.

SIGNOR-167766

P31749

P24666

0

dephosphorylation

down-regulates activity

0.321

Reduction in the levels of both LMW-PTP isoforms in vitro and in vivo increased tyrosine phosphorylation of IR and AktSer473 and increased IRS-1- and IRS-2-associated PI3-K activities in both liver and fat.|Activated PI3-K stimulates Akt (or protein kinase B) that in turn phosphorylates and inactivates glycogen synthase kinase-3

SIGNOR-248455

P05771

Q8IWA4

1

phosphorylation

down-regulates activity

0.2

Here we report that βIIPKC accumulates on the mitochondrial outer membrane and phosphorylates mitofusin 1 (Mfn1) at serine 86. Mfn1 phosphorylation results in partial loss of its GTPase activity and in a buildup of fragmented and dysfunctional mitochondria in heart failure.

SIGNOR-273826

Q13285

P28482

0

phosphorylation

up-regulates activity

0.463

Here we show that maximal SF-1-mediated transcription and interaction with general nuclear receptor cofactors depends on phosphorylation of a single serine residue (Ser-203) located in a major activation domain (AF-1) of the protein. Moreover, phosphorylation-dependent SF-1 activation is likely mediated by the mitogen-activated protein kinase (MAPK) signaling pathway.

SIGNOR-249431

P11908

P01106

0

transcriptional regulation

up-regulates quantity by expression

0.277

Analysis of in vivo C-MYC interactions with TS, IMPDH2 and PRPS2 genes confirmed that they are direct C-MYC targets. C-MYC depletion did not significantly affect levels of E2F1 protein reported to regulate expression of many S-phase specific genes, but resulted in the repression of several genes encoding enzymes rate-limiting for dNTP metabolism. These included thymidylate synthase (TS), inosine monophosphate dehydrogenase 2 (IMPDH2) and phosphoribosyl pyrophosphate synthetase 2 (PRPS2). C-MYC depletion also resulted in reduction in the amounts of deoxyribonucleoside triphosphates (dNTPs) and inhibition of proliferation.

SIGNOR-267376

P14672

P04637

0

transcriptional regulation

down-regulates quantity by repression

0.335

P53 regulates basal expression of AIF and SCO2 and facilitates oxidative phosphorylation. The expression of GLUT1, GLUT4, and HK2 is negatively regulated by p53, whereas TIGAR expression is induced by p53. The net result of p53-mediated regulation of these glycolytic enzymes is the suppression of glycolysis. In addition, p53 directly binds and inhibits G6PD activity and downregulates the pentose phosphate pathway.

SIGNOR-267465

Q68EM7

P63000

1

guanine nucleotide exchange factor

up-regulates activity

0.566

ARHGAP17 is a Rho GTPase-activating protein of Rac1

SIGNOR-272166

Q13490

O43353

1

polyubiquitination

up-regulates activity

0.652

CIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1-4).Together, our results demonstrate that depleting cIAP1/2 inhibits RIP1-4 mediated NF-kB activation without affecting RIP auto-phosphorylation.

SIGNOR-272712

Q92934

P27361

0

phosphorylation

down-regulates

0.483

Erk-1 map kinase prevents tnf-induced apoptosis through bad phosphorylation and inhibition of bax translocation in hela cells.

SIGNOR-188172

P26599

P17612

0

phosphorylation

down-regulates activity

0.309

PKA directly phosphorylates PTB on conserved Ser-16, and PKA activation in PC12 cells induces Ser-16 phosphorylation. PTB carrying a Ser-16 to alanine mutation accumulates normally in the nucleus. However, export of this mutant protein from the nucleus is greatly reduced in heterokaryon shuttling assays. Conversely, hyperphosphorylation of PTB by coexpression with the catalytic subunit of PKA results in the accumulation of PTB in the cytoplasm.

SIGNOR-263149

P12830

O14770

0

transcriptional regulation

up-regulates quantity by expression

0.2

We show that the Pbx1 and Meis2 homeodomain proteins interact with Klf4 and can be recruited to DNA elements comprising a Klf4 site or G C box, with adjacent Meis and Pbx sites. Meis2d and Pbx1a activate expression of p15(Ink4a) and E-cadherin, dependent on the Meis2d transcriptional activation domain. We suggest a model in which genes with Klf4 sites can be cooperatively activated by Meis2/Pbx1 and Klf4, dependent primarily on recruitment by Klf4.

SIGNOR-267242

Q8WY64

P01130

1

ubiquitination

down-regulates quantity by destabilization

0.723

The RING E3 ubiquitin ligase inducible degrader of the LDL receptor (IDOL, also known as MYLIP) promotes ubiquitylation and subsequent lysosomal degradation of the LDL receptor (LDLR), thus acting to limit uptake of lipoprotein-derived cholesterol into cells.

SIGNOR-271485

P49841

Q9Y4K4

0

phosphorylation

down-regulates

0.2

Gckr can phosphorylate an n-terminal recombinant fusion protein of gsk3_ and enhance the in vivo phosphorylation of gsk3_ on serine 9reduction of gckr expression inhibits wnt3a-induced phosphorylation of gsk3_ at serine 9 and decreases the accumulation of cytosolic _-catenin.

SIGNOR-148908

O95140

P45983

0

phosphorylation

down-regulates quantity

0.428

We demonstrate that a critical component of the mitochondrial fusion apparatus, the mitofusin Mfn2, is a target for phosphorylation in response to a variety of cellular stresses. We provide direct evidence that JNK mediates this phosphorylation.

SIGNOR-274138

P00519

Q70E73

1

phosphorylation

up-regulates activity

0.284

Here we show that phosphorylation of Lpd by c-Abl increases its interaction with Ena/VASP proteins. This analysis revealed that, in vitro, four Lpd peptides harboring tyrosines (Y426, Y456, Y513, Y1226) are highly phosphorylated, and eight additional peptides are phosphorylated to a lesser extent (Figure 1C).

SIGNOR-262606

P16220

Q16566

0

phosphorylation

up-regulates activity

0.708

Pka, ca2+-calmodulin-dependent kinase iv (camkiv), msk, p70s6k and rsk phosphorylate creb. All these kinases target CREB on S133 to activate CREB.

SIGNOR-102722

O95297

Q06124

0

dephosphorylation

down-regulates

0.522

In vitro, tyrosine-phosphorylated pzr was efficiently dephosphorylated by the full-length form of shp-2 but not by its sh2 domain-truncated form. The coexisting binding and dephosphorylation of pzr by shp-2 may function to terminate signal transduction initiated by pzr and shp-2 and to set a threshold for the signal transduction to be initiated.

SIGNOR-75220

Q9UQM7

Q06210

1

phosphorylation

up-regulates

0.2

Amp-activated protein kinase and calcium/calmodulin-dependent kinase ii were identified to phosphorylate specifically ser243 in vitro. Phosphorylation by these two kinases results in an increase of enzymatic activity by 1.4-fold. These findings suggest for the first time that hgfat1 may be regulated by kinases other than pka.

SIGNOR-158486

P62826

O96013

0

phosphorylation

up-regulates

0.308

We show that ran is a substrate for p21-activated kinase 4 (pak4) and that its phosphorylation on serine-135 increases during mitosis.Altogether, our findings strongly suggest that pak4-mediated phosphorylation of gdp- or gtp-bound ran modulates the assembly of complexes that are required at specific subcellular localizations for ran to carry out its functions during mitotic progression.

SIGNOR-167667

Q02078

P35580

1

transcriptional regulation

up-regulates quantity by expression

0.317

Myocyte enhancer factor-2 and serum response factor binding elements regulate fast Myosin heavy chain transcription in vivo. We show that the upstream promoter region of the gene most abundantly expressed in mouse skeletal muscles, IIb MyHC, retains binding activity and transcriptional activation for three positive transcription factors, the serum response factor, Oct-1, and myocyte enhancer factor-2, whereas the other two genes (IIa and IId/x) have nucleotide substitutions in these sites that reduce binding and transcriptional activation

SIGNOR-238763

P04004

P17252

0

phosphorylation

up-regulates quantity by stabilization

0.318

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

SIGNOR-248962

P31260

Q15910

0

transcriptional regulation

down-regulates quantity by repression

0.438

These data support the proposed regulatory impact of particular PRC2-proteins in expression of HOXA9 and HOXA10 in NK/T-cells. In mammalian cells knockdown of PRC2 components EZH2 or PHF1 led to upregulated HOXA gene expression.

SIGNOR-260070

O75688

Q9UHD2

1

dephosphorylation

down-regulates activity

0.352

PPM1B dephosphorylates TBK1 in vivo and in vitro.|These results demonstrate that PPM1B inhibits TBK1 mediated antiviral signaling by directly dephosphorylating TBK1 at Ser172.

SIGNOR-276985

Q9UBE8

P46937

1

phosphorylation

up-regulates activity

0.2

Here, we report that osmotic stress stimulates transient YAP nuclear localization and increases YAP activity even when YAP Ser127 is phosphorylated. Osmotic stress acts via the NLK kinase to induce YAP Ser128 phosphorylation. Phosphorylation of YAP at Ser128 interferes with its ability to bind to 14-3-3, resulting in YAP nuclear accumulation and induction of downstream target gene expression.

SIGNOR-273909

P06748

P24941

0

phosphorylation

down-regulates activity

0.561

Both subtypes of B23 proteins were phosphorylated during mitosis by cyclin B/cdc2. The RNA binding activity of B23.1 was repressed through cyclin B/cdc2-mediated phosphorylation at specific sites in B23. Thus, the RNA binding activity of B23.1 is stringently modulated by its phosphorylation and subtype association.

SIGNOR-89609

Q05655

P61978

1

phosphorylation

down-regulates

0.344

Ser302 is a major k protein site phosphorylated by pkcdelta in vitrothe ability of pkc_ to inducibly bind and phosphorylate k protein may serve not only to alter the activity of k protein itself, but k protein may also provide an avenue for pkc_ to engage in a cross-talk with other k protein molecular partners in response to specific changes in the extracellular environment

SIGNOR-67515

P11387

P38398

0

ubiquitination

down-regulates quantity by destabilization

0.463

Here, we show that the Ku70/Ku80 heterodimer binds with topoI, and that the DNA-dependent protein kinase (DNA-PKcs) phosphorylates topoI on serine 10 (topoI-pS10), which is subsequently ubiquitinated by BRCA1. Taken together, we conclude that BRCA1 is the E3 ligase for topoI, and the rate of topoI proteasomal degradation determines CPT response.

SIGNOR-277353

Q14814

P12882

1

transcriptional regulation

up-regulates quantity by expression

0.34

Myocyte enhancer factor-2 and serum response factor binding elements regulate fast Myosin heavy chain transcription in vivo. We show that the upstream promoter region of the gene most abundantly expressed in mouse skeletal muscles, IIb MyHC, retains binding activity and transcriptional activation for three positive transcription factors, the serum response factor, Oct-1, and myocyte enhancer factor-2, whereas the other two genes (IIa and IId/x) have nucleotide substitutions in these sites that reduce binding and transcriptional activation

SIGNOR-238751

P62805

P25440

1

relocalization

up-regulates activity

0.2

Thus, the TIP60 HAT complex is recruited to MYC-target genes and, probably with other other HATs, contributes to histone acetylation in response to mitogenic signals.

SIGNOR-262062

Q68DV7

Q14332

1

relocalization

up-regulates

0.308

Frizzled receptors are regu__lated by cycles of ubiquitylation and deubiquitylation61 (see above), and znrf3 and rnf43 act as frizzled ubiquitin ligases, removing frizzled and possibly lrp6 from the plasma membrane

SIGNOR-199585

Q92974

P27361

0

phosphorylation

up-regulates

0.29

Activates rhoa and as a result regulates actin assembly.

SIGNOR-160420

Q9NZQ7

P49840

0

phosphorylation

down-regulates quantity by destabilization

0.2

We find EGFR inhibitors promote PD-L1 ubiquitination and proteasomal degradation following GSK3α-mediated phosphorylation of Ser279/Ser283. We identify ARIH1 as the E3 ubiquitin ligase responsible for targeting PD-L1 to degradation.

SIGNOR-277552

Q2PPJ7

P31751

0

phosphorylation

down-regulates activity

0.453

RGC2 is an endogenous substrate for Akt2 downstream of PI 3-kinase

SIGNOR-269799

P11362

Q14247

1

phosphorylation

down-regulates

0.313

Cortactin, which is an actin-binding protein that also plays a role in actin cytoskeleton dynamics (45), was phosphorylated on tyr-446 in our assay (by fgfr1).Phosphorylation of these residues attenuates the f-actin cross-linking activity

SIGNOR-98618

Q13627

P04637

1

phosphorylation

up-regulates

0.417

Dyrk1a phosphorylates p53 and inhibits proliferation of embryonic neuronal cells. we found that dyrk1a phosphorylates p53 at ser-15 in vitro and in immortalized rat embryonic hippocampal progenitor h19-7 cells. In addition, dyrk1a-induced p53 phosphorylation at ser-15 led to a robust induction of p53 target genes

SIGNOR-167407

P51812

P12931

0

phosphorylation

up-regulates

0.355

Together, our findings suggest that src-dependent phosphorylation at tyr-529 facilitates inactive erk binding to rsk2, which might be a general requirement for rsk2 activation by egf through the mek/erk pathway.

SIGNOR-160052

P17612

Q9NRM7

1

phosphorylation

up-regulates

0.2

Here, we show that cyclic amp (camp)-dependent protein kinase (pka) phosphorylates lats and thereby enhances its activity sufficiently to phosphorylate yap on ser381.

SIGNOR-236994

Q9Y6R4

P52564

1

phosphorylation

up-regulates activity

0.657

When truncated mapkkk4 (deltamapkkk4) was overexpressed in hek293 cells, it was constitutively activeco-expressed map kinase kinase (mkk)-1, mkk-4, mkk-3 and mkk-6 were activated in vivo by deltamapkkk4. All of the above mkks purified from escherichia coli were phosphorylated and activated by deltamapkkk4 immunoprecipitates in vitro.

SIGNOR-62372

P52630

P49841

0

phosphorylation

down-regulates quantity by destabilization

0.289

GSK3α/β are critical kinases to regulate STAT2 protein stability mediated by FBXW7.The 4-point mutant (STAT2-4A) of STAT2 at S381A/T385A/E389A/S393A inhibited GSK3α/β-mediated STAT2 phosphorylation.

SIGNOR-276764

Q9H6Z4

Q15796

1

relocalization

down-regulates activity

0.436

RanBP3 directly recognizes dephosphorylated Smad2/3, which results from the activity of nuclear Smad phosphatases, and mediates nuclear export of Smad2/3 in a Ran-dependent manner.

SIGNOR-217634

P17612

Q92934

1

phosphorylation

down-regulates

0.542

Ser-155 is the major phosphoacceptor site for pka on bad, but that pka also phosphorylates ser-112 and ser-136. Phosphorylated bad appears to be the inactive moiety. These results implicate pkac as the candidate kinase for s112 phosphorylation in vivo.

SIGNOR-67387

Q06787

P78352

1

post transcriptional regulation

up-regulates quantity

0.473

These results point toward a novel mechanism by which FUS targets neuronal mRNA and given that these PSD-95 and Shank1 3'-UTR G quadruplex structures are also targeted by the fragile X mental retardation protein (FMRP), they raise the possibility that FUS and FMRP might work together to regulate the translation of these neuronal mRNA targets.

SIGNOR-262108

P19174

Q08881

0

phosphorylation

up-regulates

0.637

In t cells, the predominant tec kinase is itk, which functions downstream of the t-cell receptor to regulate phospholipase c-gamma.

SIGNOR-165803

P12931

O95319

1

phosphorylation

up-regulates activity

0.321

Site-directed mutagenesis of putative tyrosine phosphorylation sites in CUGBP2 identified tyrosine 39 as a c-Src target, and a CUGBP2 with a mutated tyrosine 39 displayed an attenuated ability to bind COX-2 mRNA.

SIGNOR-263195

P31751

O43524

1

phosphorylation

down-regulates activity

0.751

Akt-dependent phosphorylation of foxo3a (thr32, ser253, and ser315 for human foxo3) enhances foxo3a/14-3-3 Interaction and promotes foxo3a nuclear export to the cytoplasm, resulting in the repression of foxo3a transcriptional function akt phosphorylates members of the foxo factors (forkhead family of transcription factors), leading to binding of 14-3-3 proteins and cytoplasmic localisation. In particular, akt phosphorylates foxo1 on thr24, ser256 and ser319. Foxo 3alfa and foxo4 are phosphorylated on equivalent sites.

SIGNOR-236671

P49116

Q13131

0

phosphorylation

down-regulates

0.2

Tr4 transactivation is inhibited via phosphorylation bymetformin-induced amp-activated protein kinase (ampk) at the amino acid serine 351, which results in the suppression of scd1 gene expression

SIGNOR-173118

Q16665

P11309

0

phosphorylation

up-regulates quantity by stabilization

0.2

PIM1 kinase directly phosphorylates HIF-1α at threonine 455, a previously uncharacterized site within its oxygen-dependent degradation domain. This phosphorylation event disrupts the ability of prolyl hydroxylases to bind and hydroxylate HIF-1α, interrupting its canonical degradation pathway and promoting constitutive transcription of HIF-1 target genes.

SIGNOR-277311

P84243

O75151

0

demethylation

up-regulates activity

0.2

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

SIGNOR-264518

Q15118

P05106

1

phosphorylation

down-regulates activity

0.306

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-250264

P52566

Q8TEB7

0

polyubiquitination

up-regulates quantity by stabilization

0.2

We found that RhoGDIα and RhoGDIβ are ubiquitin E3 substrates of GRAIL. GRAIL uses nonlysine 48-ubiquitin linkage in polyubiquitinating RhoGDI. GRAIL was subsequently demonstrated to bind and ubiquitinate RhoGDI, although GRAIL-mediated ubiquitination of RhoGDI did not result in proteosomal degradation. Our data suggest that ubiquitination of RhoGDI by GRAIL does not result in proteolytic degradation. In fact, GRAIL activity appeared to increase RhoGDI stability.

SIGNOR-271621

O14733

P35568

1

phosphorylation

down-regulates activity

0.369

Tyrosine phosphorylation of IRS-1 initiates insulin signaling, whereas serine/threonine phosphorylation alters the ability of IRS-1 to transduce the insulin signalInsulin increased the phosphorylation of Ser312, Ser616, Ser636, Ser892, Ser1101, and Ser1223 Ser312 can be phosphorylated by kinases, such as c-jun NH2-terminal kinase and inhibitor of _B kinase

SIGNOR-217920

P31947

P45984

0

phosphorylation

down-regulates

0.2

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

SIGNOR-124027

P00519

P46937

1

phosphorylation

up-regulates

0.718

In this study, we show that c-abl directly phosphorylates yap1 at position y357 in response to dna damage. Tyrosine-phosphorylated yap1 is a more stable protein that displays higher affinity to p73 and selectively coactivates p73 proapoptotic target genes.

SIGNOR-160860

Q8WZ42

Q5VST9

1

relocalization

up-regulates quantity

0.58

Ankyrin-B is targeted to the M-line via its interaction with the C-terminal domain of the large sarcomeric protein obscurin. Obscurin is targeted to the M-line via its N-terminal interactions with myomesin and titin. This population of ankyrin-B recruits B56α, a regulatory subunit of protein phosphatase 2A, to the M-line where the phosphatase may regulate the phosphorylation status of contractile and signalling proteins.

SIGNOR-266728

P27361

Q12913

0

dephosphorylation

down-regulates activity

0.459

Tumor suppressor density-enhanced phosphatase-1 (DEP-1) inhibits the RAS pathway by direct dephosphorylation of ERK1/2 kinases|Pulldown and in vitro dephosphorylation assays confirmed our prediction and demonstrated an overall specificity of DEP-1 in targeting the phosphorylated tyrosine 204 of ERK1/2.

SIGNOR-248707

P68871

P15289

0

acetylation

up-regulates activity

0.2

ASA acetylates hemoglobin. Purified acetylated hemoglobin had a slightly increased oxygen affinity and decreased heme-heme interaction.

SIGNOR-251772

Q9BXM7

P62987

1

phosphorylation

up-regulates

0.385

Here we report that ubiquitin is the genuine substrate of PINK1. PINK1 phosphorylated ubiquitin at Ser 65 both in vitro and in cells, and a Ser 65 phosphopeptide derived from endogenous ubiquitin was only detected in cells in the presence of PINK1 and following a decrease in mitochondrial membrane potential.

SIGNOR-270342