GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
Q9UQM7	Q4G163	1	phosphorylation	up-regulates activity	0.403	CaMKII and polo-like kinase 1 sequentially phosphorylate the cytostatic factor Emi2/XErp1 to trigger its destruction and meiotic exit. \| these results implicate the 192RSST motif of Emi2 as a critical molecular target of CaMKII during CSF release	SIGNOR-260907
O00712	Q13562	1	transcriptional regulation	up-regulates quantity	0.282	For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)	SIGNOR-268897
P68363	Q5SQI0	0	acetylation	up-regulates quantity by stabilization	0.252	Alpha-Tubulin acetyltransferase (alphaTAT1) is the major α-tubulin lysine-40 (K40) acetyltransferase in mammals, nematodes, and protozoa, and its activity plays a conserved role in several microtubule-based processes.\|The tubulin subunits of microtubules are acetylated, and lysine-40 (K40) of the alpha-tubulin subunit has been identified as an important conserved site of microtubule acetylation (6–8). This modification is considered a hallmark of stable, long-lived microtubules	SIGNOR-272245
P0C6X7-PRO_0000037312	O75348	1	cleavage	down-regulates activity	0.2	Cleavage of the V-ATPase G1 fusion protein by SARS-CoV 3CLpro was found in this study (Fig. 3), implying that 3CLpro potentially cleaves the cellular V-ATPase G1, and affects the function of vacuolar H(+)-ATPase. Meanwhile, a significant intracellular acidification has been demonstrated in the 3CLpro-expressing cells (Fig. 4D). The result correlated well with previous reports in that V-ATPase-specific inhibitors cause acidic pHi [28], [29], and influences cell apoptosis	SIGNOR-260264
P10242	Q9UBE8	0	phosphorylation	down-regulates activity	0.714	Furthermore, the downregulation of c-Myb by NLK overexpression could be inhibited in cells that had been treated with the 26S proteasome inhibitor MG132 but not in those treated with DMSO ( ).\|HIPK2 and NLK directly bind to c-Myb, and NLK phosphorylates c-Myb at multiple sites, resulting in its ubiquitination and proteasome-dependent degradation [32].	SIGNOR-280049
Q01094	Q13535	0	phosphorylation	up-regulates quantity by stabilization	0.377	These results thus suggest that this serine 31 residue is indeed an atm/atr phosphorylation site and in fact is the major site for atm/atr-mediated phosphorylation within e2f1. Thus, it is possible that the atm/atr-mediated phosphorylation inhibits the binding and function of skp2 and thus prevents the normal degradation of e2f1	SIGNOR-109420
P19784	Q9UNN4	1	phosphorylation	up-regulates activity	0.414	ALF was able to stabilize the binding of TBP to DNA, but it could not stabilize TBP mutants A184E, N189E, E191R, and R205E nor could it facilitate binding of the TBP-like factor TRF2/TLF to a consensus TATA element. However, phosphorylation of ALF with casein kinase II resulted in the partial restoration of complex formation using mutant TBPs. \| Because the residues involved (Ser-280, Ser-281, Ser-316, and Ser-321) are conserved in ALF (Ser-356, Ser-357, Ser-418, and Ser-423), we tested whether its activity might also be affected by this modification. We first showed that ALF and TFIIAα/β polypeptides incubated with casein kinase II and [γ-32P]ATP could be labeled.	SIGNOR-250993
Q9H6E5	P35790	0	phosphorylation	up-regulates activity	0.2	Our data indicate that the kinase activities of both the isoforms of CKI -- alpha and epsilon modulate Star-PAP polyadenylation activity and target mRNAs.\|Taken together, these data suggest that phosphorylation of Star-PAP by CKI modulates the Star-PAP polyadenylation activity downstream of stimulation by oxidant stress and phosphorylation primes Star-PAP, so that it can be stimulated by PI4,5 P 2.	SIGNOR-279162
P29474	P22612	0	phosphorylation	up-regulates	0.2	Recently many investigators have shown that protein phosphorylation of enos by several serine/threonine kinases is a critical control step for no production by endothelial cells. Phosphorylation by amp kinase, akt (or protein kinase b), or protein kinase a on serine 1179 (bovine) or serine 1177 (human) of enos leads to enhanced activity of the enzyme and, thus, augmented production of no.	SIGNOR-112375
Q8IWT3	Q9BQL6	1	ubiquitination	down-regulates quantity by destabilization	0.2	M-phase-specific CDK1–cyclin B1 complex directly binds KIND1 and KIND2 and phosphorylates a conserved proline-directed CDK1 consensus motif in the flexible and intrinsically disordered loop of the F1 domain. This then results in the recruitment of the CUL9–FBXL10 complex, modification with K48-linked polyubiquitin chains and proteasomal degradation of KIND1 and KIND2.	SIGNOR-276718
Q00536	P04637	1	phosphorylation	down-regulates activity	0.386	In this study, we demonstrated that CDK16 phosphorylates p53 at Ser315 and promotes ubiquitination and subsequent degradation of p53.\|Together, these results suggest that CDK16 negatively regulates p53 stability at the post-translational level.	SIGNOR-278354
O60500	P19544	0	transcriptional regulation	up-regulates quantity by expression	0.487	The Wilms tumor suppressor gene (WT1) is a zinc-finger-containing transcription factor that is coexpressed with NPHS1 in differentiated podocytes; gel shift binding assays demonstrate that a recombinant WT1 protein can bind and activate the 186-bp NPHS1 fragment in a sequence-specific manner	SIGNOR-252299
Q6DJT9	Q09472	0	acetylation	up-regulates	0.308	Plag1 and plagl2 are also regulated by acetylation. They are acetylated and activated by p300 and deacetylated and repressed by hdac7.	SIGNOR-140915
O75385	O60260	1	phosphorylation	up-regulates activity	0.2	Furthermore, the Parkin band shift induced by catalytically active WT ULK1 was diminished by treatment of cell lysates with lambda-phosphatase, as was the mobility of ULK1 itself (XREF_FIG).\|Parkin is phosphorylated by ULK1 at Ser 108 in its recently described nine amino acid ACT element at this early time point	SIGNOR-279663
P55011	Q9H4A3	0	phosphorylation	up-regulates activity	0.491	Combining these biochemical studies with the live cell imaging data, these results collectively suggest that the entire CTD is necessary for WNK1 to drive optimal SPAK/OSR1 activation and downstream NKCC1/KCC phosphorylation via PS.	SIGNOR-277859
Q5S007	Q9UNE7	0	ubiquitination	down-regulates quantity by destabilization	0.433	CHIP can ubiquitinate LRRK2.\|These results indicate that both the chaperone interaction and the ubiquitin ligase activity of CHIP are required for CHIP mediated degradation of LRRK2 protein.	SIGNOR-278615
P08151	Q9Y297	0	ubiquitination	down-regulates quantity by destabilization	0.664	Here we show that Gli is rapidly destroyed by the proteasome and that mouse basal cell carcinoma induction correlates with Gli protein accumulation. We identify two independent destruction signals in Gli1, D(N) and D(C), and show that removal of these signals stabilizes Gli1 protein and rapidly accelerates tumor formation in transgenic animals.Levels of _TrCP appeared to be limiting for Gli1 degradation, as increasing the levels of _TrCP protein significantly decreased steady-state levels of Gli1 protein	SIGNOR-235631
P43146	P06241	0	phosphorylation	up-regulates activity	0.572	Fyn tyrosine kinase, but not Src, regulates the phosphorylation of DCC in N1E-115 neuroblastoma cells.Both DCC phosphorylation and Netrin-1-induced axon outgrowth are impaired in Fyn(-/-) CN and spinal cord explants. We propose that DCC is regulated by tyrosine phosphorylation and that Fyn is essential for the response of axons to Netrin-1. these results show that DCC is phosphorylated by Fyn, but not Src, in N1E-115 cells, and that tyrosines 1261 and 1418 are the major phosphorylation sites of Fyn in vivo.	SIGNOR-268176
P52789	P31749	0	phosphorylation	up-regulates activity	0.445	K63-linked ubiquitination enhances the interaction between Akt and HK2 and eventually increases HK2 phosphorylation on Thr473 and mitochondrial localization	SIGNOR-259984
P27448	Q8IVT5	1	phosphorylation	down-regulates activity	0.642	C-TAK1 phosphorylates KSR1 at S392, forming a 14-3-3 binding site.\|In mammalian cells, C-TAK1 has been shown to negatively regulate KSR1 by phosphorylation of Ser392.	SIGNOR-279225
P01266	P07202	0	catalytic activity	up-regulates activity	0.505	After transport through the apical membrane, I− is covalently bound to the tyrosyl residues of Tg by thyroid peroxidase (TPO).	SIGNOR-259914
Q14005	P68400	0	phosphorylation	up-regulates activity	0.326	We now show that N-terminal to the NLS domain of pro-IL-16 are protein kinase CK2 substrate and cdc2 kinase substrate sites which, along with the NLS, constitute a dual phosphorylation-regulated CcN motif which regulates nuclear localization of pro-IL-16. In addition, we demonstrate that mutation of either site is associated with impairment of the N-terminal domain's ability to induce G(0)/G(1) cell cycle arrest. \| Thus, we confirm that the N-terminal (42SLNEE46) sequence of pro-IL-16 is in fact a site for protein kinase CK2 phosphorylation.	SIGNOR-250905
P46459	Q5S007	0	phosphorylation	up-regulates activity	0.367	LRRK2 phosphorylates full-length NSF at threonine 645 in the ATP binding pocket of D2 domain. Functionally, NSF phosphorylated by LRRK2 displays enhanced ATPase activity and increased rate of SNARE complex disassembling.	SIGNOR-277196
Q96LD4	Q9NQC7	1	ubiquitination	down-regulates quantity	0.2	CYLD is progressively degraded upon interaction with the E3 ligase TRIM47 in proportion to NASH severity	SIGNOR-266443
Q2TAL8	P26640	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-269408
O15297	P06493	0	phosphorylation	down-regulates quantity by destabilization	0.348	Phosphorylation of multiple residues in the catalytic domain of PPM1D during mitosis, including Ser40 by Cyclin-dependent kinase 1 (CDK1), leads to ubiquitination of PPM1D and subsequent proteasomal degradation by Adenomatous polyposis coli (APC) and cell-division cycle protein 20 (CDC20)	SIGNOR-275489
P68400	O60936	1	phosphorylation	up-regulates activity	0.324	Phosphorylation of ARC at T149 Is Required for Its Antiapoptotic Effect. Here we report that the function of ARC is regulated by protein kinase CK2. ARC at threonine 149 is phosphorylated by CK2. This phosphorylation targets ARC to mitochondria. ARC is able to bind to caspase-8 only when it is localized to mitochondria but not to the cytoplasm.	SIGNOR-262837
P24844	Q13464	0	phosphorylation	up-regulates	0.646	Rho-kinase phosphorylates the mlc of intact myosin and activates its mgatpase activity in a gtp_?Rho-dependent manner.	SIGNOR-43031
Q9UJD0	O14795	1	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
P15374	Q13315	0	phosphorylation	up-regulates activity	0.331	Mechanistically, in response to DNA damage, the deubiquitinase UCHL3 is phosphorylated and activated by ATM.	SIGNOR-279794
O15151	O96017	0	phosphorylation	down-regulates	0.723	Phosphorylation of s342 and s367 in vivo require the chk2 kinase. Chk2 also stimulates mdmx ubiquitination and degradation by mdm2	SIGNOR-140417
Q14653	P67775	0	dephosphorylation	down-regulates activity	0.314	RACK1 Negatively Regulates the Type I IFN pathway. Here we report that IRF3 is deactivated via dephosphorylation mediated by the serine and threonine phosphatase PP2A and its adaptor protein RACK1. The PP2A-RACK1 complex negatively regulated the IRF3 pathway after LPS or poly(I:C) stimulation or Sendai virus (SeV) infection.	SIGNOR-260944
Q96Q27	P27361	0	phosphorylation	up-regulates activity	0.265	Indeed, using mass spectrometry, we showed for the first time that ASB2a is phosphorylated and that phosphorylation of serine-323 (Ser-323) of ASB2a is crucial for the targeting of the actin-binding protein filamin A (FLNa) to degradation. \|Moreover, inhibition of the extracellular signal-regulated kinases 1 and 2 (Erk1/2) activity reduced ASB2a-mediated FLNa degradation.	SIGNOR-272241
Q16543	P68400	0	phosphorylation	up-regulates activity	0.397	Phosphorylation of serine 13 is required for the proper function of the Hsp90 co-chaperone, Cdc37. \| In this report, we demonstrate that mammalian Cdc37 is phosphorylated on Ser13 in situ in rabbit reticulocyte lysate and in cultured K562 cells and that casein kinase II is capable of quantitatively phosphorylating recombinant Cdc37 at this site.	SIGNOR-250838
P28482	P49137	1	phosphorylation	up-regulates	0.507	Using novel methodology we demonstrate that activation of mapkap kinase-2 requires the phosphorylation of any two of the three residues thr222, ser272 and thr334. gst-mapkap kinase-2 lacking the n-terminal domain was inactive, but activated fully when phosphorylated at thr222, ser272 and thr334 by p42 mapk or rk.	SIGNOR-44343
Q8IVS8	P27361	0	phosphorylation	up-regulates quantity by stabilization	0.2	Mechanistically, glucose deprivation-activated ERK1 phosphorylates GLYCTK2 at serine 220 directly, which prevents STUB1 (ubiquitin E3 ligase) binding, thereby abrogating the ubiquitination and degradation of GLYCTK2. ERK1 phosphorylates GLYCTK2 at S220 to promotes its stability	SIGNOR-280257
P22681	Q13882	0	phosphorylation	down-regulates activity	0.488	Herein we report that PTK6 phosphorylates and down-regulates E3 ubiquitin ligase c-Cbl.	SIGNOR-279348
P17252	P14598	1	phosphorylation	up-regulates	0.553	Phosphopeptide mapping of p47(phox) showed that, as opposed to pkc zeta, pkc alpha, beta ii, and delta are able to phosphorylate all the major pkc sites. The use of p47(phox) mutants identified serines 303, 304, 315, 320, 328, 359, 370, and 379 as targets of pkc alpha, beta ii, and delta.Taken together, these results suggest that pkc alpha, beta ii, delta, and zeta expressed in human neutrophils can individually phosphorylate p47(phox) and induce both its translocation and nadph oxidase activation.	SIGNOR-89178
Q99986	P48431	1	phosphorylation	up-regulates activity	0.468	VRK1, but not kinase-dead VRK1 (K179E), phosphorylated Sox2 (XREF_FIG).	SIGNOR-279578
P00519	Q9H3D4	1	phosphorylation	up-regulates quantity by stabilization	0.543	In cell lines, upon cisplatin treatment, c-Abl phosphorylates TAp63 on specific tyrosine residues. Such modifications affect p63 stability and induce a p63-dependent activation of proapoptotic promoters.	SIGNOR-260934
Q13043	P52945	1	phosphorylation	down-regulates activity	0.2	MST1 directly phosphorylated PDX1 at Thr11, resulting in its ubiquitination, degradation and impaired insulin secretion.\|Thus, kinase activity is required for MST1 induced PDX1 degradation.	SIGNOR-278303
Q15303	Q00535	0	phosphorylation	up-regulates activity	0.278	Cdk5 Promotes ErbB4 and PI3-Kinase Activity In Vivo.\|Cdk5 phosphorylates ErbB4 at T1152, situated in close proximity to the PI3-kinase-binding site (Y1056), and in turn promotes ErbB4 tyrosine phosphorylation.	SIGNOR-278436
P20336	Q9UQ26	0	relocalization	up-regulates activity	0.762	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-264377
Q15858	P06241	0	phosphorylation	up-regulates activity	0.363	Our results demonstrate Fyn -mediated upregulation of Nav1.7 protein expression and tyrosine phosphorylation and identify two tyrosine residues within the DIII-DIV linker (L3) as Fyn phosphorylation sites.	SIGNOR-279614
Q9Y297	Q53EL6	1	ubiquitination	down-regulates	0.425	Both akt and p70(s6k) phosphorylate pdcd4, allowing for binding of the e3-ubiquitin ligase beta-trcp and consequently ubiquitylation.	SIGNOR-160985
P45983	P05787	1	phosphorylation	up-regulates	0.375	Kinase assays showed that c-jun n-terminal kinase (jnk) was also activated with activation kinetics corresponding to that of k8 phosphorylation. Furthermore, k8 was also phosphorylated on ser-73 by jnk in vitro. The ser-73 --> ala-associated filament reorganization defect is rescued by a ser-73 --> asp mutation. Also, disease-causing keratin mutations can modulate keratin phosphorylation and organization, which may affect disease pathogenesis.	SIGNOR-113645
Q9Y6B2	Q00987	0	polyubiquitination	down-regulates quantity by destabilization	0.424	Degradation of EID-1 occurs via ubiquitin-dependent proteolysis and correlates with MDM2 binding. These results are consistent with a model wherein destruction of EID-1 is linked to its ability to interact with MDM2 via either p300 or pRB.	SIGNOR-272582
P31751	Q09472	1	phosphorylation	up-regulates	0.327	We find that suberoylanilide hydroxamic acid stimulates akt activity, which is required to phosphorylate p300 at ser(1834). Akt-mediated phosphorylation of p300 dramatically increases its acetyltransferase activity	SIGNOR-148987
P60484	P06213	0	phosphorylation	down-regulates activity	0.442	Our results show that the kinase region of IRβ subunit physically binds to PTEN and phosphorylates on Y27 and Y174. In the current study, we discovered that IR also downregulates PTEN through tyrosine phosphorylation and suggest that Y27 and 174 are the two key tyrosines.	SIGNOR-276470
Q9H2X6	Q9Y6I7	0	ubiquitination	down-regulates	0.568	Ubiquitination and degradation of homeodomain-interacting protein kinase 2 by wd40 repeat/socs box protein wsb-1	SIGNOR-160032
P10721	Q06124	1	phosphorylation	up-regulates activity	0.684	SHP2 can be phosphorylated at 2 C-terminal tyrosyl residues by receptor tyrosine kinases, including KIT as well as cytosolic tyrosine kinases, including Src and Abl. The level of tyrosyl phosphorylation of SHP2 has been associated with its recruitment to the receptor.Thus, pharmacologic inhibition of SHP2 phosphatase function might permit SHP2 to return to its inactive conformation resulting in reduced tyrosine phosphorylation.	SIGNOR-256140
Q96QC0	O60285	0	phosphorylation	up-regulates activity	0.2	Here, we show that NUAK1 is a predominantly nuclear protein that associates with a network of nuclear protein phosphatase 1 (PP1) interactors and that PNUTS, a nuclear regulatory subunit of PP1, is phosphorylated by NUAK1.\|Inhibition of NUAK1 abolishes chromatin association of PNUTS, reduces spliceosome activity, and suppresses nascent RNA synthesis.	SIGNOR-280051
P23769	Q969H0	0	ubiquitination	down-regulates quantity by destabilization	0.388	Here, we demonstrate that F-box/WD repeat-containing protein 7 (Fbw7/Fbxw7), a component of Skp1, Cullin 1, F-box-containing complex (SCF)-type E3 ligase, is an E3 ligase for GATA2. GATA2 contains a cell division control protein 4 (Cdc4) phosphodegron (CPD), a consensus motif for ubiquitylation by Fbw7, which includes Thr(176). Ectopic expression of Fbw7 destabilized GATA2 and promoted its proteasomal degradation.	SIGNOR-256005
P35398	P48539	1	transcriptional regulation	up-regulates quantity by expression	0.2	RORα regulates the expression of several genes in Purkinje cells. RORα becomes highly expressed in postmitotic Purkinje cells. It regulates their maturation, particularly dendritic differentiation. Dendritogenesis and the expression of several genes, including Shh, Itpr1, Pcp4, Calb1, Pcp2, and Slc1a6, normally expressed in mature Purkinje cells, are inhibited in RORα-deficient mice.	SIGNOR-266848
P04179	Q9P275	0	deubiquitination	up-regulates quantity by stabilization	0.319	Protein stability of mitochondrial superoxide dismutase SOD2 is regulated by USP36\|Finally, USP36 was shown to be a specific deubiquitinating enzyme that reduces the ubiquitination level of SOD2 and was involved in SOD2 protein stability by extending its half-life.	SIGNOR-272280
Q05655	P08913	1	phosphorylation	up-regulates activity	0.533	Taken together, these results indicate that S232 acts as a selective, PKC-sensitive, modulator of effector coupling of the alpha(2A)AR to inositol phosphate stimulation. This represents one mechanism by which cells route stimuli directed to multifunctional receptors to selected effectors so as to attain finely targeted signaling.	SIGNOR-249126
Q92918	P43405	0	phosphorylation	up-regulates activity	0.348	BCR ligation induced rapid tyrosine-phosphorylation of HPK1 mainly by Syk and Lyn, resulting in its association with BASH and catalytic activation. BCR-mediated activation of HPK1 was impaired in Syk- or BASH-deficient B cells. The functional SH2 domain of BASH and Tyr-379 within HPK1 which we identified as a Syk-phosphorylation site were both necessary for interaction of both proteins and efficient HPK1 activation after BCR stimulation.	SIGNOR-246567
P04792	P31751	0	phosphorylation	down-regulates	0.289	First, the akt1, akt2, and akt3 isoforms can bind directly to hsp27 and can be found in a complex with p38 mapk, mk2, and hsp27 [98_100]. Second, rane and colleagues showed that akt could phosphorylate hsp27 at ser-82, but not ser-15 or ser-78, in vitro, while co-expression of an active akt mutant and hsp27 in hek cells resulted in hsp27 phosphorylation at the same residue.	SIGNOR-186776
Q05655	Q01995	1	phosphorylation	down-regulates activity	0.327	Of the three consensus protein kinase C or casein kinase II phosphorylation sites in SM22, only Ser-181 was readily phosphorylated by protein kinase C in vitro, and such phosphorylation greatly decreased actin binding.	SIGNOR-249061
P25098	O95398	1	phosphorylation	down-regulates activity	0.2	The observation that GRK2 co-immunoprecipitates with Epac1 suggests a direct association between GRK2 and Epac1 in DRGs. xref A detailed study of the influence of GRK2 on the Epac1 level found that phosphorylation of ser108 in Epac1 by GRK2 can lead to a reduction of Epac1 activation. xref Downstream consequence of a reduction of GRK2 was explored. xref Low GRK2 expression in GRK2(\u00b1) DRGs was found to facilitate CPT-induced Rap1 activation and increase the phosphorylated ERK1/2 level.	SIGNOR-280001
P49841	P17655	0	cleavage	up-regulates activity	0.285	Thus, it has been shown that calpain cleaves the inhibitory domain of GSK3 generating two fragments of 40 and 30 kDa. This cleavage enhanced activity of the kinase	SIGNOR-251613
P68400	P37840	1	phosphorylation	up-regulates	0.514	In vitro experiments and two-dimensional phosphopeptide mapping provided further evidence that serine 129 was phosphorylated by ck-1 and ck-2. Moreover, phosphorylation of serine 129 was reduced in vivo upon inhibition of ck-1 or ck-2. These data demonstrate that alpha-synuclein is constitutively phosphorylated within its c terminus and may indicate that the function of alpha-synuclein is regulated by phosphorylation/dephosphorylation.From these data we conclude that _-synuclein is predominantly phosphorylated at serine residue 129. However, a second serine at position 87 is also used for phosphorylation to some extent. together, these data may indicate that ck-1 and ck-2 are involved in the regulation of neuronal function and one may speculate that phosphorylation of _-synuclein could affect its binding to membranes.	SIGNOR-73807
Q8N122	P27361	0	phosphorylation	up-regulates activity	0.469	We found three proline-directed residues within raptor, ser(8), ser(696), and ser(863), which are directly phosphorylated by erk1/2. Expression of phosphorylation-deficient alleles of raptor revealed that phosphorylation of these sites by erk1/2 normally promotes mtorc1 activity and signaling to downstream substrates, such as 4e-bp1.	SIGNOR-169530
P43405	P07948	0	phosphorylation	up-regulates activity	0.61	Lyn phosphorylates and activates Syk and LAT.	SIGNOR-279415
P25098	P35372	1	phosphorylation	down-regulates activity	0.2	These results suggest that two C-terminal amino acids, Ser(355) and Thr(357), are required for short-term homologous desensitization and agonist-induced phosphorylation of mu-opioid receptors expressed in HEK 293 cells	SIGNOR-249661
Q13315	Q9NRR5	1	phosphorylation	up-regulates activity	0.2	These results suggest that UBQLN4 phosphorylation on S318 is functionally important for its role in the DSB response.>Particularly HRR is dependent on ATM activity (Dietlein et al., 2014). Here, we showed that UBQLN4 is an ATM substrate and that DSB sealing is markedly impaired in UBQLN4-depleted cells. HRR depends on a 5′-3′ DSB end resection, which is initiated by the MRE11 nuclease	SIGNOR-265076
Q7Z6Z7	Q86YD1	1	ubiquitination	down-regulates quantity	0.2	Our data suggest that HUWE1 can ubiquitinate PTOV1 in vitro and depletion of HUWE1 in cells increases the stability of PTOV1 S36A protein in the nucleus.\|Our data suggest that depletion of HUWE1 elevates PTOV1 protein levels, which, in turn, promote the expression of cJun, a pro-growth translational target of PTOV1 (18)\n In our model, we propose that HUWE1 mediates the degradation of PTOV1 in the nucleus.	SIGNOR-278755
Q15418	Q92882	1	phosphorylation	down-regulates activity	0.352	SH3P2 was phosphorylated on Ser(202) by ribosomal S6 kinase (RSK) in an ERK pathway-dependent manner, and such phosphorylation inhibited the ability of SH3P2 to suppress cell motility.	SIGNOR-273838
P27694	Q9UMS4	0	polyubiquitination	up-regulates activity	0.509	PRP19 is a ubiquitin ligase involved in pre-mRNA splicing and the DNA damage response (DDR). PRP19 ubiquitylates RPA and promotes ATRIP recruitment.	SIGNOR-272076
Q9NR28	P53779	0	phosphorylation	down-regulates	0.341	Here we demonstrate that jnk3 can phosphorylate smac. Phosphorylation of smac by jnk3 attenuates its interaction with xiap. These results suggest that jnk3 activity can attenuate the progression of apoptosis through a novel mechanism of action, the down-regulation of interaction between smac and xiap.	SIGNOR-157280
Q05655	P51828	1	phosphorylation	up-regulates activity	0.555	Immunoprecipitation data indicated that PKCdelta could bind and directly phosphorylate AC7.	SIGNOR-279258
O15455	P12931	0	phosphorylation	up-regulates activity	0.526	Markedly, Src mediated late TLR3 Pi-Tyr759 leads to the nuclear accumulation of IRF3 and IRF7 and the increase of IFN-beta production.\|Src can directly phosphorylate TLR3 Tyr759 in\nvitro and in vivo .	SIGNOR-279657
Q07812	Q15818	0	relocalization	up-regulates activity	0.2	Immunofluorescence staining and subcellular fractionation analyses revealed increased mitochondrial translocation of Bad and Bax proteins from cytoplasm following OGD (4 h) and simultaneously increased release of Cyt C from mitochondria followed by activation of caspase-3. NP1 protein was immunoprecipitated with Bad and Bax proteins; OGD caused increased interactions of NP1 with Bad and Bax, thereby, facilitating their mitochondrial translocation and dissipation of mitochondrial membrane potential	SIGNOR-261439
P30279	P01106	0	transcriptional regulation	up-regulates quantity by expression	0.45	C-myc directly activates transcription of cyclin d1, cyclin d2 and cdk4, and leads to cdk 4/6 activation.	SIGNOR-27446
P49770	P41091	1	guanine nucleotide exchange factor	up-regulates activity	0.696	EIF2B converts the protein synthesis initiation factor 2 (eIF2) from an inactive GDP-bound form to an active eIF2-GTP complex owing to its guanine nucleotide exchange factor (GEF) activity.	SIGNOR-269135
Q12778	Q13153	0	phosphorylation	down-regulates activity	0.358	Pak1 efficiently phosphorylated GST-FKHR.	SIGNOR-279242
P45984	P19419	1	phosphorylation	up-regulates activity	0.49	However, both of these stimuli strongly activate two other mapks, jnk1 and jnk2, and stimulate elk-1 transcriptional activity and phosphorylation jnk phosphorylation sites include ser383 and ser389, the major residues whose phosphorylation is responsible for enhancement of elk-1 trascriptional activity.	SIGNOR-247062
Q2TAL8	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-269413
Q05655	O00165	1	phosphorylation	down-regulates quantity by destabilization	0.2	FBXO25 encodes an orphan F-box protein that determines the substrate specificity of the SCF (SKP1-CUL1-F-box)(FBXO25) ubiquitin ligase complex. An unbiased screen uncovered the prosurvival protein HCLS1-associated protein X-1 (HAX-1) as the bona fide substrate of FBXO25 that is targeted after apoptotic stresses. Protein kinase Cdelta (PRKCD) initiates this process by phosphorylating FBXO25 and HAX-1, thereby spatially directing nuclear FBXO25 to mitochondrial HAX-1.\|Accordingly, PRKCD-induced phosphorylation of Hax-1 at Ser210 and Fbxo25 at Ser178 was associated with decreased expression of Hax-1 in control cells,	SIGNOR-275562
P01106	P04818	1	transcriptional regulation	up-regulates quantity by expression	0.337	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-267374
Q12809	Q15139	0	phosphorylation	down-regulates activity	0.2	Based on LC-MS results from in vivo and HEK293 cell experiments we chose four KV11.1 mutant candidates for further functional analysis. Ablation of the putative PKD phosphorylation site in the mutant S284A increased the maximal current indicating S284 as a main PKD target in KV11.1.	SIGNOR-277612
Q9UNE7	Q9UPR3	1	polyubiquitination	down-regulates quantity by destabilization	0.398	Here, we report that the human ortholog of the yeast ever-shorter telomeres 1B (EST1B) binds HDAC8. This interaction is regulated by protein kinase A-mediated HDAC8 phosphorylation and protects human EST1B (hEST1B) from ubiquitin-mediated degradation. Phosphorylated HDAC8 preferentially recruits Hsp70 to a complex that inhibits the CHIP (C-terminal heat shock protein interacting protein) E3 ligase-mediated degradation of hEST1B.	SIGNOR-272649
P35222	Q12913	0	dephosphorylation	up-regulates activity	0.519	Our data demonstrate that CD148 promotes E-cadherin cell adhesion by regulating Rac1 activity, concomitant with modulation of p120, \u03b2-catenin, and Src tyrosine phosphorylation, and that this effect requires E-cadherin and p120 association.\|Taken together, it is likely that CD148 dephosphorylation of \u03b2-catenin enhances the cadherin cell adhesion independent of Rho family GTPases.	SIGNOR-276992
P24385	Q9Y463	0	phosphorylation	down-regulates	0.41	Further, we found that not only gsk-3beta but also dyrk1b modulates cyclin d1 subcellular localization by the phosphorylation of thr(288). These results suggest that dif-3 induces degradation of cyclin d1 through the gsk-3beta- and dyrk1b-mediated threonine phosphorylation in hela cells	SIGNOR-150126
P05787	Q05655	0	phosphorylation	up-regulates	0.322	The present study showed that shear stress, but not stretch, activates PKC delta and phosphorylates K8 Ser-73, which then mediates the disassembly/reorganization of keratin IF in AEC.	SIGNOR-260887
Q15418	Q92934	1	phosphorylation	down-regulates activity	0.395	We report here that the phosphorylation of BAD at Ser-155 within the BH3 domain is a second phosphorylation-dependent mechanism that inhibits the death-promoting activity of BAD. Protein kinase A, RSK1, and survival factor signaling stimulate phosphorylation of BAD at Ser-155, blocking the binding of BAD to Bcl-XL. RSK1 phosphorylates BAD at both Ser-112 and Ser-155 and rescues BAD-mediated cell death in a manner dependent upon phosphorylation at both sites.	SIGNOR-249045
Q969R2	P49841	0	phosphorylation	up-regulates activity	0.2	CK1a1, JNK1 and CDK1 had the highest site-specific activity for ORP4L, while CDK1, GSK3a, CK1a1 and GSK3b showed the highest specificity for the site when corrected for background activity with ORP4L-S4A. Because of the complexity of the serine/proline-rich site, we did not determine which serine(s) in ORP4L were phosphorylated by candidate kinases.\|We conclude that phosphorylation of a unique serine/proline motif in the ORD induces a conformation change in ORP4L that enhances interaction with vimentin and cholesterol extraction from membranes.	SIGNOR-264874
Q15185	P68400	0	phosphorylation	up-regulates	0.354	Several lines of evidence suggest that a cpges-activating protein kinase is ck-ii (casein kinase ii). Recombinant cpges was phosphorylated directly by and associated with ck-ii in vitro, resulting in marked reduction of the k m for the substrate pgh2.	SIGNOR-123594
P50402	P12931	0	phosphorylation	down-regulates	0.451	Src phosphorylated emerin specifically at y59, y74 and y95; interestingly y-to-f substitutions at identified src sites reduced recombinant emerin binding to endogenous baf	SIGNOR-188308
P55072	Q5VZV1	0	methylation	up-regulates activity	0.308	We reveal that METTL21C trimethylates p97 on the Lys315 residue and found that loss of this modification reduced p97 hexamer formation and ATPase activity in vivo.	SIGNOR-255918
Q00535	Q8IWR1	1	phosphorylation	up-regulates activity	0.2	Here, we identify TRIM59 as a substrate of CDK5. EGFR-activated CDK5 directly binds to and phosphorylates TRIM59, a ubiquitin ligase at serine 308, which recruits PIN1 for cis-trans isomerization of TRIM59, leading to TRIM59 binding to importin α5 and nuclear translocation.	SIGNOR-272929
Q04760	P22455	0	phosphorylation	up-regulates activity	0.2	We show that Glo1 activity is promoted by phosphorylation on Tyrosine 136 via multiple kinases. Glo1 Y136 is phosphorylated by multiple different kinases including all members of the Src family. Depletion of multiple different kinases led to a partial reduction in Glo1(Y136) phosphorylation. These included members of the Src family (Src, Yes1, FGR, and the related Abl1), and of the FAK, EPHA, FGFR, and VEGFR families (Figure 2B), suggesting phosphorylation of Glo1 on Y136 by multiple different kinases. In vitro kinase assays revealed that all the members of the Src family, as well as Epha5 and VEGFR3, can efficiently phosphorylate recombinant Glo1 on Y136 (Figure 2C–D).	SIGNOR-276182
Q9C0C7	O15111	0	phosphorylation	up-regulates activity	0.2	Furthermore, we show that mitophagy function of AMBRA1 is post-translationally controlled, upon HUWE1 activity, by a positive phosphorylation on its serine 1014. This modification is mediated by the IKKα kinase and induces structural changes in AMBRA1, thus promoting its interaction with LC3/GABARAP (mATG8) proteins and its mitophagic activity.	SIGNOR-272974
O15169	P62140	0	dephosphorylation	down-regulates activity	0.2	The data suggest that PP1 controls Wnt signaling through interaction with, and regulated dephosphorylation of, axin\| Axin phosphorylation markedly enhances the binding of glycogen synthase kinase 3, leading to a more active beta-catenin destruction complex. Wnt-regulated changes in axin phosphorylation, mediated by PP1, may therefore determine beta-catenin transcriptional activity\| Four sites, S80, S82, S222, and S473, were identified to be PP1 regulated	SIGNOR-248567
P16104	P45983	0	phosphorylation	up-regulates	0.2	The stress-response kinase jnk1, activated by dna damage and initiating a pro-apoptotic program, has been recently shown to translocate into the nucleus upon activation where it phosphorylates substrates including h2ax s139, an event critical for dna degradation mediated by caspase-activated dnase (cad) in apoptotic cells	SIGNOR-184146
Q8IYT8	A2RUS2	1	phosphorylation	up-regulates activity	0.2	ULK-mediated phosphorylation of the guanine nucleotide exchange factor DENND3 at serines 554 and 572 upregulates its GEF activity toward the small GTPase Rab12.	SIGNOR-264733
Q13043	Q14653	1	phosphorylation	up-regulates activity	0.2	Beyond that, another investigation demonstrated that MST1 directly phosphorylated IRF3 at T75 and T253, which disrupted the dimerization of IRF3 and restrained RLRs and cGAS-mediated innate antiviral response.	SIGNOR-280145
P17706	P01116	1	dephosphorylation	down-regulates activity	0.276	Mechanistically, PTPN2 negatively regulates tyrosine phosphorylation of KRAS, which, in turn, affects the activation KRAS and its downstream signaling.	SIGNOR-277039
P62136	Q00987	1	dephosphorylation	up-regulates quantity by stabilization	0.356	Three phosphorylation sites identified are Ser342, Ser367, and Ser403. In the present study, we identify protein phosphatase 1 (PP1) as a negative regulator in the p53 signaling pathway. PP1 directly interacts with Mdmx and specifically dephosphorylates Mdmx at Ser367. The dephosphorylation of Mdmx increases its stability and thereby inhibits p53 activity.	SIGNOR-248566
O43318	Q6P589	1	phosphorylation	down-regulates quantity by destabilization	0.2	TAK1 phosphorylated the Ser3 in the noncanonical degron motif of TIPE2 to trigger its interaction with β-TrCP for subsequent ubiquitination and degradation.	SIGNOR-273668

Q9UQM7

Q4G163

1

phosphorylation

up-regulates activity

0.403

CaMKII and polo-like kinase 1 sequentially phosphorylate the cytostatic factor Emi2/XErp1 to trigger its destruction and meiotic exit. | these results implicate the 192RSST motif of Emi2 as a critical molecular target of CaMKII during CSF release

SIGNOR-260907

O00712

Q13562

1

transcriptional regulation

up-regulates quantity

0.282

For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)

SIGNOR-268897

P68363

Q5SQI0

0

acetylation

up-regulates quantity by stabilization

0.252

Alpha-Tubulin acetyltransferase (alphaTAT1) is the major α-tubulin lysine-40 (K40) acetyltransferase in mammals, nematodes, and protozoa, and its activity plays a conserved role in several microtubule-based processes.|The tubulin subunits of microtubules are acetylated, and lysine-40 (K40) of the alpha-tubulin subunit has been identified as an important conserved site of microtubule acetylation (6–8). This modification is considered a hallmark of stable, long-lived microtubules

SIGNOR-272245

P0C6X7-PRO_0000037312

O75348

1

cleavage

down-regulates activity

0.2

Cleavage of the V-ATPase G1 fusion protein by SARS-CoV 3CLpro was found in this study (Fig. 3), implying that 3CLpro potentially cleaves the cellular V-ATPase G1, and affects the function of vacuolar H(+)-ATPase. Meanwhile, a significant intracellular acidification has been demonstrated in the 3CLpro-expressing cells (Fig. 4D). The result correlated well with previous reports in that V-ATPase-specific inhibitors cause acidic pHi [28], [29], and influences cell apoptosis

SIGNOR-260264

P10242

Q9UBE8

0

phosphorylation

down-regulates activity

0.714

Furthermore, the downregulation of c-Myb by NLK overexpression could be inhibited in cells that had been treated with the 26S proteasome inhibitor MG132 but not in those treated with DMSO ( ).|HIPK2 and NLK directly bind to c-Myb, and NLK phosphorylates c-Myb at multiple sites, resulting in its ubiquitination and proteasome-dependent degradation [32].

SIGNOR-280049

Q01094

Q13535

0

phosphorylation

up-regulates quantity by stabilization

0.377

These results thus suggest that this serine 31 residue is indeed an atm/atr phosphorylation site and in fact is the major site for atm/atr-mediated phosphorylation within e2f1. Thus, it is possible that the atm/atr-mediated phosphorylation inhibits the binding and function of skp2 and thus prevents the normal degradation of e2f1

SIGNOR-109420

P19784

Q9UNN4

1

phosphorylation

up-regulates activity

0.414

ALF was able to stabilize the binding of TBP to DNA, but it could not stabilize TBP mutants A184E, N189E, E191R, and R205E nor could it facilitate binding of the TBP-like factor TRF2/TLF to a consensus TATA element. However, phosphorylation of ALF with casein kinase II resulted in the partial restoration of complex formation using mutant TBPs. | Because the residues involved (Ser-280, Ser-281, Ser-316, and Ser-321) are conserved in ALF (Ser-356, Ser-357, Ser-418, and Ser-423), we tested whether its activity might also be affected by this modification. We first showed that ALF and TFIIAα/β polypeptides incubated with casein kinase II and [γ-32P]ATP could be labeled.

SIGNOR-250993

Q9H6E5

P35790

0

phosphorylation

up-regulates activity

0.2

Our data indicate that the kinase activities of both the isoforms of CKI -- alpha and epsilon modulate Star-PAP polyadenylation activity and target mRNAs.|Taken together, these data suggest that phosphorylation of Star-PAP by CKI modulates the Star-PAP polyadenylation activity downstream of stimulation by oxidant stress and phosphorylation primes Star-PAP, so that it can be stimulated by PI4,5 P 2.

SIGNOR-279162

P29474

P22612

0

phosphorylation

up-regulates

0.2

Recently many investigators have shown that protein phosphorylation of enos by several serine/threonine kinases is a critical control step for no production by endothelial cells. Phosphorylation by amp kinase, akt (or protein kinase b), or protein kinase a on serine 1179 (bovine) or serine 1177 (human) of enos leads to enhanced activity of the enzyme and, thus, augmented production of no.

SIGNOR-112375

Q8IWT3

Q9BQL6

1

ubiquitination

down-regulates quantity by destabilization

0.2

M-phase-specific CDK1–cyclin B1 complex directly binds KIND1 and KIND2 and phosphorylates a conserved proline-directed CDK1 consensus motif in the flexible and intrinsically disordered loop of the F1 domain. This then results in the recruitment of the CUL9–FBXL10 complex, modification with K48-linked polyubiquitin chains and proteasomal degradation of KIND1 and KIND2.

SIGNOR-276718

Q00536

P04637

1

phosphorylation

down-regulates activity

0.386

In this study, we demonstrated that CDK16 phosphorylates p53 at Ser315 and promotes ubiquitination and subsequent degradation of p53.|Together, these results suggest that CDK16 negatively regulates p53 stability at the post-translational level.

SIGNOR-278354

O60500

P19544

0

transcriptional regulation

up-regulates quantity by expression

0.487

The Wilms tumor suppressor gene (WT1) is a zinc-finger-containing transcription factor that is coexpressed with NPHS1 in differentiated podocytes; gel shift binding assays demonstrate that a recombinant WT1 protein can bind and activate the 186-bp NPHS1 fragment in a sequence-specific manner

SIGNOR-252299

Q6DJT9

Q09472

0

acetylation

up-regulates

0.308

Plag1 and plagl2 are also regulated by acetylation. They are acetylated and activated by p300 and deacetylated and repressed by hdac7.

SIGNOR-140915

O75385

O60260

1

phosphorylation

up-regulates activity

0.2

Furthermore, the Parkin band shift induced by catalytically active WT ULK1 was diminished by treatment of cell lysates with lambda-phosphatase, as was the mobility of ULK1 itself (XREF_FIG).|Parkin is phosphorylated by ULK1 at Ser 108 in its recently described nine amino acid ACT element at this early time point

SIGNOR-279663

P55011

Q9H4A3

0

phosphorylation

up-regulates activity

0.491

Combining these biochemical studies with the live cell imaging data, these results collectively suggest that the entire CTD is necessary for WNK1 to drive optimal SPAK/OSR1 activation and downstream NKCC1/KCC phosphorylation via PS.

SIGNOR-277859

Q5S007

Q9UNE7

0

ubiquitination

down-regulates quantity by destabilization

0.433

CHIP can ubiquitinate LRRK2.|These results indicate that both the chaperone interaction and the ubiquitin ligase activity of CHIP are required for CHIP mediated degradation of LRRK2 protein.

SIGNOR-278615

P08151

Q9Y297

0

ubiquitination

down-regulates quantity by destabilization

0.664

Here we show that Gli is rapidly destroyed by the proteasome and that mouse basal cell carcinoma induction correlates with Gli protein accumulation. We identify two independent destruction signals in Gli1, D(N) and D(C), and show that removal of these signals stabilizes Gli1 protein and rapidly accelerates tumor formation in transgenic animals.Levels of _TrCP appeared to be limiting for Gli1 degradation, as increasing the levels of _TrCP protein significantly decreased steady-state levels of Gli1 protein

SIGNOR-235631

P43146

P06241

0

phosphorylation

up-regulates activity

0.572

Fyn tyrosine kinase, but not Src, regulates the phosphorylation of DCC in N1E-115 neuroblastoma cells.Both DCC phosphorylation and Netrin-1-induced axon outgrowth are impaired in Fyn(-/-) CN and spinal cord explants. We propose that DCC is regulated by tyrosine phosphorylation and that Fyn is essential for the response of axons to Netrin-1. these results show that DCC is phosphorylated by Fyn, but not Src, in N1E-115 cells, and that tyrosines 1261 and 1418 are the major phosphorylation sites of Fyn in vivo.

SIGNOR-268176

P52789

P31749

0

phosphorylation

up-regulates activity

0.445

K63-linked ubiquitination enhances the interaction between Akt and HK2 and eventually increases HK2 phosphorylation on Thr473 and mitochondrial localization

SIGNOR-259984

P27448

Q8IVT5

1

phosphorylation

down-regulates activity

0.642

C-TAK1 phosphorylates KSR1 at S392, forming a 14-3-3 binding site.|In mammalian cells, C-TAK1 has been shown to negatively regulate KSR1 by phosphorylation of Ser392.

SIGNOR-279225

P01266

P07202

0

catalytic activity

up-regulates activity

0.505

After transport through the apical membrane, I− is covalently bound to the tyrosyl residues of Tg by thyroid peroxidase (TPO).

SIGNOR-259914

Q14005

P68400

0

phosphorylation

up-regulates activity

0.326

We now show that N-terminal to the NLS domain of pro-IL-16 are protein kinase CK2 substrate and cdc2 kinase substrate sites which, along with the NLS, constitute a dual phosphorylation-regulated CcN motif which regulates nuclear localization of pro-IL-16. In addition, we demonstrate that mutation of either site is associated with impairment of the N-terminal domain's ability to induce G(0)/G(1) cell cycle arrest. | Thus, we confirm that the N-terminal (42SLNEE46) sequence of pro-IL-16 is in fact a site for protein kinase CK2 phosphorylation.

SIGNOR-250905

P46459

Q5S007

0

phosphorylation

up-regulates activity

0.367

LRRK2 phosphorylates full-length NSF at threonine 645 in the ATP binding pocket of D2 domain. Functionally, NSF phosphorylated by LRRK2 displays enhanced ATPase activity and increased rate of SNARE complex disassembling.

SIGNOR-277196

Q96LD4

Q9NQC7

1

ubiquitination

down-regulates quantity

0.2

CYLD is progressively degraded upon interaction with the E3 ligase TRIM47 in proportion to NASH severity

SIGNOR-266443

Q2TAL8

P26640

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-269408

O15297

P06493

0

phosphorylation

down-regulates quantity by destabilization

0.348

Phosphorylation of multiple residues in the catalytic domain of PPM1D during mitosis, including Ser40 by Cyclin-dependent kinase 1 (CDK1), leads to ubiquitination of PPM1D and subsequent proteasomal degradation by Adenomatous polyposis coli (APC) and cell-division cycle protein 20 (CDC20)

SIGNOR-275489

P68400

O60936

1

phosphorylation

up-regulates activity

0.324

Phosphorylation of ARC at T149 Is Required for Its Antiapoptotic Effect. Here we report that the function of ARC is regulated by protein kinase CK2. ARC at threonine 149 is phosphorylated by CK2. This phosphorylation targets ARC to mitochondria. ARC is able to bind to caspase-8 only when it is localized to mitochondria but not to the cytoplasm.

SIGNOR-262837

P24844

Q13464

0

phosphorylation

up-regulates

0.646

Rho-kinase phosphorylates the mlc of intact myosin and activates its mgatpase activity in a gtp_?Rho-dependent manner.

SIGNOR-43031

Q9UJD0

O14795

1

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

P15374

Q13315

0

phosphorylation

up-regulates activity

0.331

Mechanistically, in response to DNA damage, the deubiquitinase UCHL3 is phosphorylated and activated by ATM.

SIGNOR-279794

O15151

O96017

0

phosphorylation

down-regulates

0.723

Phosphorylation of s342 and s367 in vivo require the chk2 kinase. Chk2 also stimulates mdmx ubiquitination and degradation by mdm2

SIGNOR-140417

Q14653

P67775

0

dephosphorylation

down-regulates activity

0.314

RACK1 Negatively Regulates the Type I IFN pathway. Here we report that IRF3 is deactivated via dephosphorylation mediated by the serine and threonine phosphatase PP2A and its adaptor protein RACK1. The PP2A-RACK1 complex negatively regulated the IRF3 pathway after LPS or poly(I:C) stimulation or Sendai virus (SeV) infection.

SIGNOR-260944

Q96Q27

P27361

0

phosphorylation

up-regulates activity

0.265

Indeed, using mass spectrometry, we showed for the first time that ASB2a is phosphorylated and that phosphorylation of serine-323 (Ser-323) of ASB2a is crucial for the targeting of the actin-binding protein filamin A (FLNa) to degradation. |Moreover, inhibition of the extracellular signal-regulated kinases 1 and 2 (Erk1/2) activity reduced ASB2a-mediated FLNa degradation.

SIGNOR-272241

Q16543

P68400

0

phosphorylation

up-regulates activity

0.397

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

SIGNOR-250838

P28482

P49137

1

phosphorylation

up-regulates

0.507

Using novel methodology we demonstrate that activation of mapkap kinase-2 requires the phosphorylation of any two of the three residues thr222, ser272 and thr334. gst-mapkap kinase-2 lacking the n-terminal domain was inactive, but activated fully when phosphorylated at thr222, ser272 and thr334 by p42 mapk or rk.

SIGNOR-44343

Q8IVS8

P27361

0

phosphorylation

up-regulates quantity by stabilization

0.2

Mechanistically, glucose deprivation-activated ERK1 phosphorylates GLYCTK2 at serine 220 directly, which prevents STUB1 (ubiquitin E3 ligase) binding, thereby abrogating the ubiquitination and degradation of GLYCTK2. ERK1 phosphorylates GLYCTK2 at S220 to promotes its stability

SIGNOR-280257

P22681

Q13882

0

phosphorylation

down-regulates activity

0.488

Herein we report that PTK6 phosphorylates and down-regulates E3 ubiquitin ligase c-Cbl.

SIGNOR-279348

P17252

P14598

1

phosphorylation

up-regulates

0.553

Phosphopeptide mapping of p47(phox) showed that, as opposed to pkc zeta, pkc alpha, beta ii, and delta are able to phosphorylate all the major pkc sites. The use of p47(phox) mutants identified serines 303, 304, 315, 320, 328, 359, 370, and 379 as targets of pkc alpha, beta ii, and delta.Taken together, these results suggest that pkc alpha, beta ii, delta, and zeta expressed in human neutrophils can individually phosphorylate p47(phox) and induce both its translocation and nadph oxidase activation.

SIGNOR-89178

Q99986

P48431

1

phosphorylation

up-regulates activity

0.468

VRK1, but not kinase-dead VRK1 (K179E), phosphorylated Sox2 (XREF_FIG).

SIGNOR-279578

P00519

Q9H3D4

1

phosphorylation

up-regulates quantity by stabilization

0.543

In cell lines, upon cisplatin treatment, c-Abl phosphorylates TAp63 on specific tyrosine residues. Such modifications affect p63 stability and induce a p63-dependent activation of proapoptotic promoters.

SIGNOR-260934

Q13043

P52945

1

phosphorylation

down-regulates activity

0.2

MST1 directly phosphorylated PDX1 at Thr11, resulting in its ubiquitination, degradation and impaired insulin secretion.|Thus, kinase activity is required for MST1 induced PDX1 degradation.

SIGNOR-278303

Q15303

Q00535

0

phosphorylation

up-regulates activity

0.278

Cdk5 Promotes ErbB4 and PI3-Kinase Activity In Vivo.|Cdk5 phosphorylates ErbB4 at T1152, situated in close proximity to the PI3-kinase-binding site (Y1056), and in turn promotes ErbB4 tyrosine phosphorylation.

SIGNOR-278436

P20336

Q9UQ26

0

relocalization

up-regulates activity

0.762

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-264377

Q15858

P06241

0

phosphorylation

up-regulates activity

0.363

Our results demonstrate Fyn -mediated upregulation of Nav1.7 protein expression and tyrosine phosphorylation and identify two tyrosine residues within the DIII-DIV linker (L3) as Fyn phosphorylation sites.

SIGNOR-279614

Q9Y297

Q53EL6

1

ubiquitination

down-regulates

0.425

Both akt and p70(s6k) phosphorylate pdcd4, allowing for binding of the e3-ubiquitin ligase beta-trcp and consequently ubiquitylation.

SIGNOR-160985

P45983

P05787

1

phosphorylation

up-regulates

0.375

Kinase assays showed that c-jun n-terminal kinase (jnk) was also activated with activation kinetics corresponding to that of k8 phosphorylation. Furthermore, k8 was also phosphorylated on ser-73 by jnk in vitro. The ser-73 --> ala-associated filament reorganization defect is rescued by a ser-73 --> asp mutation. Also, disease-causing keratin mutations can modulate keratin phosphorylation and organization, which may affect disease pathogenesis.

SIGNOR-113645

Q9Y6B2

Q00987

0

polyubiquitination

down-regulates quantity by destabilization

0.424

Degradation of EID-1 occurs via ubiquitin-dependent proteolysis and correlates with MDM2 binding. These results are consistent with a model wherein destruction of EID-1 is linked to its ability to interact with MDM2 via either p300 or pRB.

SIGNOR-272582

P31751

Q09472

1

phosphorylation

up-regulates

0.327

We find that suberoylanilide hydroxamic acid stimulates akt activity, which is required to phosphorylate p300 at ser(1834). Akt-mediated phosphorylation of p300 dramatically increases its acetyltransferase activity

SIGNOR-148987

P60484

P06213

0

phosphorylation

down-regulates activity

0.442

Our results show that the kinase region of IRβ subunit physically binds to PTEN and phosphorylates on Y27 and Y174. In the current study, we discovered that IR also downregulates PTEN through tyrosine phosphorylation and suggest that Y27 and 174 are the two key tyrosines.

SIGNOR-276470

Q9H2X6

Q9Y6I7

0

ubiquitination

down-regulates

0.568

Ubiquitination and degradation of homeodomain-interacting protein kinase 2 by wd40 repeat/socs box protein wsb-1

SIGNOR-160032

P10721

Q06124

1

phosphorylation

up-regulates activity

0.684

SHP2 can be phosphorylated at 2 C-terminal tyrosyl residues by receptor tyrosine kinases, including KIT as well as cytosolic tyrosine kinases, including Src and Abl. The level of tyrosyl phosphorylation of SHP2 has been associated with its recruitment to the receptor.Thus, pharmacologic inhibition of SHP2 phosphatase function might permit SHP2 to return to its inactive conformation resulting in reduced tyrosine phosphorylation.

SIGNOR-256140

Q96QC0

O60285

0

phosphorylation

up-regulates activity

0.2

Here, we show that NUAK1 is a predominantly nuclear protein that associates with a network of nuclear protein phosphatase 1 (PP1) interactors and that PNUTS, a nuclear regulatory subunit of PP1, is phosphorylated by NUAK1.|Inhibition of NUAK1 abolishes chromatin association of PNUTS, reduces spliceosome activity, and suppresses nascent RNA synthesis.

SIGNOR-280051

P23769

Q969H0

0

ubiquitination

down-regulates quantity by destabilization

0.388

Here, we demonstrate that F-box/WD repeat-containing protein 7 (Fbw7/Fbxw7), a component of Skp1, Cullin 1, F-box-containing complex (SCF)-type E3 ligase, is an E3 ligase for GATA2. GATA2 contains a cell division control protein 4 (Cdc4) phosphodegron (CPD), a consensus motif for ubiquitylation by Fbw7, which includes Thr(176). Ectopic expression of Fbw7 destabilized GATA2 and promoted its proteasomal degradation.

SIGNOR-256005

P35398

P48539

1

transcriptional regulation

up-regulates quantity by expression

0.2

RORα regulates the expression of several genes in Purkinje cells. RORα becomes highly expressed in postmitotic Purkinje cells. It regulates their maturation, particularly dendritic differentiation. Dendritogenesis and the expression of several genes, including Shh, Itpr1, Pcp4, Calb1, Pcp2, and Slc1a6, normally expressed in mature Purkinje cells, are inhibited in RORα-deficient mice.

SIGNOR-266848

P04179

Q9P275

0

deubiquitination

up-regulates quantity by stabilization

0.319

Protein stability of mitochondrial superoxide dismutase SOD2 is regulated by USP36|Finally, USP36 was shown to be a specific deubiquitinating enzyme that reduces the ubiquitination level of SOD2 and was involved in SOD2 protein stability by extending its half-life.

SIGNOR-272280

Q05655

P08913

1

phosphorylation

up-regulates activity

0.533

Taken together, these results indicate that S232 acts as a selective, PKC-sensitive, modulator of effector coupling of the alpha(2A)AR to inositol phosphate stimulation. This represents one mechanism by which cells route stimuli directed to multifunctional receptors to selected effectors so as to attain finely targeted signaling.

SIGNOR-249126

Q92918

P43405

0

phosphorylation

up-regulates activity

0.348

BCR ligation induced rapid tyrosine-phosphorylation of HPK1 mainly by Syk and Lyn, resulting in its association with BASH and catalytic activation. BCR-mediated activation of HPK1 was impaired in Syk- or BASH-deficient B cells. The functional SH2 domain of BASH and Tyr-379 within HPK1 which we identified as a Syk-phosphorylation site were both necessary for interaction of both proteins and efficient HPK1 activation after BCR stimulation.

SIGNOR-246567

P04792

P31751

0

phosphorylation

down-regulates

0.289

First, the akt1, akt2, and akt3 isoforms can bind directly to hsp27 and can be found in a complex with p38 mapk, mk2, and hsp27 [98_100]. Second, rane and colleagues showed that akt could phosphorylate hsp27 at ser-82, but not ser-15 or ser-78, in vitro, while co-expression of an active akt mutant and hsp27 in hek cells resulted in hsp27 phosphorylation at the same residue.

SIGNOR-186776

Q05655

Q01995

1

phosphorylation

down-regulates activity

0.327

Of the three consensus protein kinase C or casein kinase II phosphorylation sites in SM22, only Ser-181 was readily phosphorylated by protein kinase C in vitro, and such phosphorylation greatly decreased actin binding.

SIGNOR-249061

P25098

O95398

1

phosphorylation

down-regulates activity

0.2

The observation that GRK2 co-immunoprecipitates with Epac1 suggests a direct association between GRK2 and Epac1 in DRGs. xref A detailed study of the influence of GRK2 on the Epac1 level found that phosphorylation of ser108 in Epac1 by GRK2 can lead to a reduction of Epac1 activation. xref Downstream consequence of a reduction of GRK2 was explored. xref Low GRK2 expression in GRK2(\u00b1) DRGs was found to facilitate CPT-induced Rap1 activation and increase the phosphorylated ERK1/2 level.

SIGNOR-280001

P49841

P17655

0

cleavage

up-regulates activity

0.285

Thus, it has been shown that calpain cleaves the inhibitory domain of GSK3 generating two fragments of 40 and 30 kDa. This cleavage enhanced activity of the kinase

SIGNOR-251613

P68400

P37840

1

phosphorylation

up-regulates

0.514

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

SIGNOR-73807

Q8N122

P27361

0

phosphorylation

up-regulates activity

0.469

We found three proline-directed residues within raptor, ser(8), ser(696), and ser(863), which are directly phosphorylated by erk1/2. Expression of phosphorylation-deficient alleles of raptor revealed that phosphorylation of these sites by erk1/2 normally promotes mtorc1 activity and signaling to downstream substrates, such as 4e-bp1.

SIGNOR-169530

P43405

P07948

0

phosphorylation

up-regulates activity

0.61

Lyn phosphorylates and activates Syk and LAT.

SIGNOR-279415

P25098

P35372

1

phosphorylation

down-regulates activity

0.2

These results suggest that two C-terminal amino acids, Ser(355) and Thr(357), are required for short-term homologous desensitization and agonist-induced phosphorylation of mu-opioid receptors expressed in HEK 293 cells

SIGNOR-249661

Q13315

Q9NRR5

1

phosphorylation

up-regulates activity

0.2

These results suggest that UBQLN4 phosphorylation on S318 is functionally important for its role in the DSB response.>Particularly HRR is dependent on ATM activity (Dietlein et al., 2014). Here, we showed that UBQLN4 is an ATM substrate and that DSB sealing is markedly impaired in UBQLN4-depleted cells. HRR depends on a 5′-3′ DSB end resection, which is initiated by the MRE11 nuclease

SIGNOR-265076

Q7Z6Z7

Q86YD1

1

ubiquitination

down-regulates quantity

0.2

Our data suggest that HUWE1 can ubiquitinate PTOV1 in vitro and depletion of HUWE1 in cells increases the stability of PTOV1 S36A protein in the nucleus.|Our data suggest that depletion of HUWE1 elevates PTOV1 protein levels, which, in turn, promote the expression of cJun, a pro-growth translational target of PTOV1 (18)\n In our model, we propose that HUWE1 mediates the degradation of PTOV1 in the nucleus.

SIGNOR-278755

Q15418

Q92882

1

phosphorylation

down-regulates activity

0.352

SH3P2 was phosphorylated on Ser(202) by ribosomal S6 kinase (RSK) in an ERK pathway-dependent manner, and such phosphorylation inhibited the ability of SH3P2 to suppress cell motility.

SIGNOR-273838

P27694

Q9UMS4

0

polyubiquitination

up-regulates activity

0.509

PRP19 is a ubiquitin ligase involved in pre-mRNA splicing and the DNA damage response (DDR). PRP19 ubiquitylates RPA and promotes ATRIP recruitment.

SIGNOR-272076

Q9NR28

P53779

0

phosphorylation

down-regulates

0.341

Here we demonstrate that jnk3 can phosphorylate smac. Phosphorylation of smac by jnk3 attenuates its interaction with xiap. These results suggest that jnk3 activity can attenuate the progression of apoptosis through a novel mechanism of action, the down-regulation of interaction between smac and xiap.

SIGNOR-157280

Q05655

P51828

1

phosphorylation

up-regulates activity

0.555

Immunoprecipitation data indicated that PKCdelta could bind and directly phosphorylate AC7.

SIGNOR-279258

O15455

P12931

0

phosphorylation

up-regulates activity

0.526

Markedly, Src mediated late TLR3 Pi-Tyr759 leads to the nuclear accumulation of IRF3 and IRF7 and the increase of IFN-beta production.|Src can directly phosphorylate TLR3 Tyr759 in\nvitro and in vivo .

SIGNOR-279657

Q07812

Q15818

0

relocalization

up-regulates activity

0.2

Immunofluorescence staining and subcellular fractionation analyses revealed increased mitochondrial translocation of Bad and Bax proteins from cytoplasm following OGD (4 h) and simultaneously increased release of Cyt C from mitochondria followed by activation of caspase-3. NP1 protein was immunoprecipitated with Bad and Bax proteins; OGD caused increased interactions of NP1 with Bad and Bax, thereby, facilitating their mitochondrial translocation and dissipation of mitochondrial membrane potential

SIGNOR-261439

P30279

P01106

0

transcriptional regulation

up-regulates quantity by expression

0.45

C-myc directly activates transcription of cyclin d1, cyclin d2 and cdk4, and leads to cdk 4/6 activation.

SIGNOR-27446

P49770

P41091

1

guanine nucleotide exchange factor

up-regulates activity

0.696

EIF2B converts the protein synthesis initiation factor 2 (eIF2) from an inactive GDP-bound form to an active eIF2-GTP complex owing to its guanine nucleotide exchange factor (GEF) activity.

SIGNOR-269135

Q12778

Q13153

0

phosphorylation

down-regulates activity

0.358

Pak1 efficiently phosphorylated GST-FKHR.

SIGNOR-279242

P45984

P19419

1

phosphorylation

up-regulates activity

0.49

However, both of these stimuli strongly activate two other mapks, jnk1 and jnk2, and stimulate elk-1 transcriptional activity and phosphorylation jnk phosphorylation sites include ser383 and ser389, the major residues whose phosphorylation is responsible for enhancement of elk-1 trascriptional activity.

SIGNOR-247062

Q2TAL8

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-269413

Q05655

O00165

1

phosphorylation

down-regulates quantity by destabilization

0.2

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

SIGNOR-275562

P01106

P04818

1

transcriptional regulation

up-regulates quantity by expression

0.337

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-267374

Q12809

Q15139

0

phosphorylation

down-regulates activity

0.2

Based on LC-MS results from in vivo and HEK293 cell experiments we chose four KV11.1 mutant candidates for further functional analysis. Ablation of the putative PKD phosphorylation site in the mutant S284A increased the maximal current indicating S284 as a main PKD target in KV11.1.

SIGNOR-277612

Q9UNE7

Q9UPR3

1

polyubiquitination

down-regulates quantity by destabilization

0.398

Here, we report that the human ortholog of the yeast ever-shorter telomeres 1B (EST1B) binds HDAC8. This interaction is regulated by protein kinase A-mediated HDAC8 phosphorylation and protects human EST1B (hEST1B) from ubiquitin-mediated degradation. Phosphorylated HDAC8 preferentially recruits Hsp70 to a complex that inhibits the CHIP (C-terminal heat shock protein interacting protein) E3 ligase-mediated degradation of hEST1B.

SIGNOR-272649

P35222

Q12913

0

dephosphorylation

up-regulates activity

0.519

Our data demonstrate that CD148 promotes E-cadherin cell adhesion by regulating Rac1 activity, concomitant with modulation of p120, \u03b2-catenin, and Src tyrosine phosphorylation, and that this effect requires E-cadherin and p120 association.|Taken together, it is likely that CD148 dephosphorylation of \u03b2-catenin enhances the cadherin cell adhesion independent of Rho family GTPases.

SIGNOR-276992

P24385

Q9Y463

0

phosphorylation

down-regulates

0.41

Further, we found that not only gsk-3beta but also dyrk1b modulates cyclin d1 subcellular localization by the phosphorylation of thr(288). These results suggest that dif-3 induces degradation of cyclin d1 through the gsk-3beta- and dyrk1b-mediated threonine phosphorylation in hela cells

SIGNOR-150126

P05787

Q05655

0

phosphorylation

up-regulates

0.322

The present study showed that shear stress, but not stretch, activates PKC delta and phosphorylates K8 Ser-73, which then mediates the disassembly/reorganization of keratin IF in AEC.

SIGNOR-260887

Q15418

Q92934

1

phosphorylation

down-regulates activity

0.395

We report here that the phosphorylation of BAD at Ser-155 within the BH3 domain is a second phosphorylation-dependent mechanism that inhibits the death-promoting activity of BAD. Protein kinase A, RSK1, and survival factor signaling stimulate phosphorylation of BAD at Ser-155, blocking the binding of BAD to Bcl-XL. RSK1 phosphorylates BAD at both Ser-112 and Ser-155 and rescues BAD-mediated cell death in a manner dependent upon phosphorylation at both sites.

SIGNOR-249045

Q969R2

P49841

0

phosphorylation

up-regulates activity

0.2

CK1a1, JNK1 and CDK1 had the highest site-specific activity for ORP4L, while CDK1, GSK3a, CK1a1 and GSK3b showed the highest specificity for the site when corrected for background activity with ORP4L-S4A. Because of the complexity of the serine/proline-rich site, we did not determine which serine(s) in ORP4L were phosphorylated by candidate kinases.|We conclude that phosphorylation of a unique serine/proline motif in the ORD induces a conformation change in ORP4L that enhances interaction with vimentin and cholesterol extraction from membranes.

SIGNOR-264874

Q15185

P68400

0

phosphorylation

up-regulates

0.354

Several lines of evidence suggest that a cpges-activating protein kinase is ck-ii (casein kinase ii). Recombinant cpges was phosphorylated directly by and associated with ck-ii in vitro, resulting in marked reduction of the k m for the substrate pgh2.

SIGNOR-123594

P50402

P12931

0

phosphorylation

down-regulates

0.451

Src phosphorylated emerin specifically at y59, y74 and y95; interestingly y-to-f substitutions at identified src sites reduced recombinant emerin binding to endogenous baf

SIGNOR-188308

P55072

Q5VZV1

0

methylation

up-regulates activity

0.308

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

SIGNOR-255918

Q00535

Q8IWR1

1

phosphorylation

up-regulates activity

0.2

Here, we identify TRIM59 as a substrate of CDK5. EGFR-activated CDK5 directly binds to and phosphorylates TRIM59, a ubiquitin ligase at serine 308, which recruits PIN1 for cis-trans isomerization of TRIM59, leading to TRIM59 binding to importin α5 and nuclear translocation.

SIGNOR-272929

Q04760

P22455

0

phosphorylation

up-regulates activity

0.2

We show that Glo1 activity is promoted by phosphorylation on Tyrosine 136 via multiple kinases. Glo1 Y136 is phosphorylated by multiple different kinases including all members of the Src family. Depletion of multiple different kinases led to a partial reduction in Glo1(Y136) phosphorylation. These included members of the Src family (Src, Yes1, FGR, and the related Abl1), and of the FAK, EPHA, FGFR, and VEGFR families (Figure 2B), suggesting phosphorylation of Glo1 on Y136 by multiple different kinases. In vitro kinase assays revealed that all the members of the Src family, as well as Epha5 and VEGFR3, can efficiently phosphorylate recombinant Glo1 on Y136 (Figure 2C–D).

SIGNOR-276182

Q9C0C7

O15111

0

phosphorylation

up-regulates activity

0.2

Furthermore, we show that mitophagy function of AMBRA1 is post-translationally controlled, upon HUWE1 activity, by a positive phosphorylation on its serine 1014. This modification is mediated by the IKKα kinase and induces structural changes in AMBRA1, thus promoting its interaction with LC3/GABARAP (mATG8) proteins and its mitophagic activity.

SIGNOR-272974

O15169

P62140

0

dephosphorylation

down-regulates activity

0.2

The data suggest that PP1 controls Wnt signaling through interaction with, and regulated dephosphorylation of, axin| Axin phosphorylation markedly enhances the binding of glycogen synthase kinase 3, leading to a more active beta-catenin destruction complex. Wnt-regulated changes in axin phosphorylation, mediated by PP1, may therefore determine beta-catenin transcriptional activity| Four sites, S80, S82, S222, and S473, were identified to be PP1 regulated

SIGNOR-248567

P16104

P45983

0

phosphorylation

up-regulates

0.2

The stress-response kinase jnk1, activated by dna damage and initiating a pro-apoptotic program, has been recently shown to translocate into the nucleus upon activation where it phosphorylates substrates including h2ax s139, an event critical for dna degradation mediated by caspase-activated dnase (cad) in apoptotic cells

SIGNOR-184146

Q8IYT8

A2RUS2

1

phosphorylation

up-regulates activity

0.2

ULK-mediated phosphorylation of the guanine nucleotide exchange factor DENND3 at serines 554 and 572 upregulates its GEF activity toward the small GTPase Rab12.

SIGNOR-264733

Q13043

Q14653

1

phosphorylation

up-regulates activity

0.2

Beyond that, another investigation demonstrated that MST1 directly phosphorylated IRF3 at T75 and T253, which disrupted the dimerization of IRF3 and restrained RLRs and cGAS-mediated innate antiviral response.

SIGNOR-280145

P17706

P01116

1

dephosphorylation

down-regulates activity

0.276

Mechanistically, PTPN2 negatively regulates tyrosine phosphorylation of KRAS, which, in turn, affects the activation KRAS and its downstream signaling.

SIGNOR-277039

P62136

Q00987

1

dephosphorylation

up-regulates quantity by stabilization

0.356

Three phosphorylation sites identified are Ser342, Ser367, and Ser403. In the present study, we identify protein phosphatase 1 (PP1) as a negative regulator in the p53 signaling pathway. PP1 directly interacts with Mdmx and specifically dephosphorylates Mdmx at Ser367. The dephosphorylation of Mdmx increases its stability and thereby inhibits p53 activity.

SIGNOR-248566

O43318

Q6P589

1

phosphorylation

down-regulates quantity by destabilization

0.2

TAK1 phosphorylated the Ser3 in the noncanonical degron motif of TIPE2 to trigger its interaction with β-TrCP for subsequent ubiquitination and degradation.

SIGNOR-273668