GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
P57764	P51878	0	cleavage	up-regulates activity	0.62	Co-expression of GSDMD with caspase-1, 4, 5 or 11 but not apoptotic caspases (caspase-2, 8 and 9) in 293T cells induced the same cleavage of GSDMD\|inflammatory caspases specifically cleave GSDMD after the 272FLTD275 (or 273LLSD276) sequence \|	SIGNOR-256418
Q99942	P49023	1	ubiquitination	down-regulates quantity	0.407	Here we demonstrate that the human homologue of RNF5 associates with the amino-terminal domain of paxillin, resulting in its ubiquitination. RNF5 requires intact RING and C-terminal domains to mediate paxillin ubiquitination. Concomitantly, RNF5 expression results in inhibition of cell motility. Via targeting of paxillin ubiquitination, which alters its localization, RNF5 emerges as a novel regulator of cell motility.	SIGNOR-271479
O15111	Q9BUZ4	1	phosphorylation	down-regulates	0.384	Traf4 is atypical within its family because it is the only traf family member to negatively regulate innate immune signaling. Ikk_'s phosphorylation of serine-426 on traf4 was required for this negative regulation.	SIGNOR-197253
Q13546	P21580	0	ubiquitination	down-regulates quantity	0.655	The amino-terminal domain of A20, which is a de-ubiquitinating (DUB) enzyme of the OTU (ovarian tumour) family, removes lysine-63 (K63)-linked ubiquitin chains from receptor interacting protein (RIP), an essential mediator of the proximal TNF receptor 1 (TNFR1) signalling complex. The carboxy-terminal domain of A20, composed of seven C2/C2 zinc fingers, then functions as a ubiquitin ligase by polyubiquitinating RIP with K48-linked ubiquitin chains, thereby targeting RIP for proteasomal degradation.	SIGNOR-259978
P06493	Q13501	1	phosphorylation	up-regulates	0.343	Here we show that cdk1 phosphorylates p62 in vitro and in vivo at t269 and s272, which is necessary for the maintenance of appropriate cyclin b1 levels and the levels of cdk1 activity necessary to allow cells to properly enter and exit mitosis.	SIGNOR-169012
Q13224	Q00535	0	phosphorylation	down-regulates quantity	0.443	Cdk5 phosphorylates NR2B at Ser1116 and controls surface level expression.\|Reduction in Cdk5 activity, as well as disruption of Cdk5-NR2B interactions consistently increased NR2B surface levels and facilitated NMDA mediated synaptic function.	SIGNOR-278265
O00429	Q9GZY8	0	relocalization	up-regulates activity	0.601	Mff functions as an essential factor in mitochondrial recruitment of Drp1.	SIGNOR-245957
P78362	Q9UKV3	1	phosphorylation	up-regulates	0.476	Here, we show that srpk2 binds and phosphorylates acinus, an sr protein essential for rna splicing, and redistributes it from the nuclear speckles to the nucleoplasm, resulting in cyclin a1 but not a2 up-regulation. Acinus s422d, an srpk2 phosphorylation mimetic, enhances cyclin a1 transcription, whereas acinus s422a, an unphosphorylatable mutant, blocks the stimulatory effect of srpk2	SIGNOR-179006
O60566	Q12834	1	phosphorylation	up-regulates activity	0.993	Furthermore, BUBR1 phosphorylates p55CDC in vitro, and the phosphorylation of p55CDC by BUBR1 appears to be correlated with spindle checkpoint activation.	SIGNOR-279507
Q04760	P22607	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-276181
P04637	P49841	0	phosphorylation	up-regulates activity	0.728	Glycogen synthase kinase3 beta phosphorylates serine 33 of p53 and activates p53's transcriptional activity.	SIGNOR-251258
Q96PU5	Q9C0H2	1	polyubiquitination	down-regulates quantity by destabilization	0.2	Our data indicate that Nedd4-2 binds to two family members, TTYH2 and TTYH3, which contain consensus PY ((L/P)PXY) binding sites for HECT type E3 ubiquitin ligases, but not to TTYH1, which lacks this motif. Consistently, Nedd4-2 ubiquitinates both TTYH2 and TTYH3. Importantly, we have shown that endogenous TTYH2 and Nedd4-2 are binding partners and demonstrated that the TTYH2 PY motif is essential for these interactions. We have also shown that Nedd4-2-mediated ubiquitination of TTYH2 is a critical regulator of cell surface and total cellular levels of this protein.	SIGNOR-272633
Q14674	O60216	1	cleavage	down-regulates quantity by destabilization	0.78	In order to segregate sister chromatids to opposite poles in anaphase, cohesin has to be removed from chromosomes. In budding yeast, the prevalent mode of cohesin removal is by proteolytic cleavage of the Scc1 subunit at the onset of anaphase by the endopeptidase separase	SIGNOR-275537
O96013	P28698	1	phosphorylation	up-regulates activity	0.2	Here, we link ErbB2 activation to invasion via ErbB2-induced, SUMO-directed phosphorylation of a single serine residue, S27, of the transcription factor myeloid zinc finger-1 (MZF1). Phosphorylation of MZF1-S27 is an early response to ErbB2 activation and results in increased transcriptional activity of MZF1.The phosphorylation of MZF1-S27 is preceded by poly-SUMOylation of K23, which can make S27 accessible to efficient phosphorylation by PAK4.	SIGNOR-277422
Q13501	Q9Y4E8	0	deubiquitination	down-regulates activity	0.26	SQSTM1 Is a Substrate for RNF26 and the DUB USP15. Catalytically competent RNF26 (light red) recruits SQSTM1 (blue) and mediates ubiquitin ligation (red), which serves to attract UBDs of specific vesicle-associated adaptors. Dissociation of the RNF26/SQSTM1 complex, promoted by the DUB USP15 (yellow), releases target vesicles for (4) fast transport into the cell periphery.	SIGNOR-269829
P10415	Q15173	0	dephosphorylation	down-regulates	0.323	Pp2a directly interacts with the bh4 domain of bcl2 as a docking site to potentially bridge pp2a to bcl2's flexible loop domain containing the target serine 70 phosphorylation site.	SIGNOR-181559
Q05655	P62714	0	dephosphorylation	down-regulates activity	0.3	PP2A(c) displayed the highest specific activity towards PKCdelta. The role of PP2A(c) in the dephosphorylation of PKCdelta in cells was supported by the demonstration that these proteins could be co-immunoprecipitated from NIH3T3 cells.\|In conclusion, the evidence here indicates that PKCdelta de-phosphorylation and hence inactivation is effected by PP2A with which it forms a complex	SIGNOR-248595
Q15831	Q15418	0	phosphorylation	down-regulates activity	0.288	Negative regulation of the LKB1/AMPK pathway by ERK in human acute myeloid leukemia cellsBRAFV600E activates downstream molecules, including ERK and p90 ribosomal S6 kinase (RSK), and leads to the phosphorylation of LKB-1 at Ser428 by these kinases. This cascade results in the dissociation of LKB1 from AMPK.	SIGNOR-209871
O14641	Q96GF1	0	polyubiquitination	down-regulates quantity by destabilization	0.466	The E3 ligase RNF185 negatively regulates osteogenic differentiation by targeting Dvl2 for degradation. Overexpression of RNF185 decreases the exogenous and endogenous level of Dvl2, promotes the ubiquitination and degradation of Dvl2	SIGNOR-272173
Q8N2H9	Q15306	1	ubiquitination	down-regulates activity	0.2	Peli3 induces the degradation of IRF4 through K48‐mediated ubiquitination \|To detect the direct interaction of Peli3 and IRF4, Peli3 and IRF4 DNA constructs were transfected into HEK293 cells.	SIGNOR-280453
Q05519	P02649	1	post transcriptional regulation	up-regulates quantity by stabilization	0.2	We demonstrate that SFRS11 directly binds to the 3' UTR of LRP8 mRNA, as well as to the third exon of apoE mRNA, resulting in stabilization of these mRNAs, eventually deactivating JNK signaling.	SIGNOR-269671
P01111	P49842	0	phosphorylation	up-regulates activity	0.306	STK19 Phosphorylates NRAS Protein at Serine 89\|STK19 phosphorylates NRAS to enhance its binding to its downstream effectors and promotes oncogenic NRAS-mediated melanocyte malignant transformation.\|	SIGNOR-264566
Q14195	P49841	0	phosphorylation	up-regulates activity	0.475	Together, these results suggest that crmp4 is able to increase neurite formation and elongation in neurons, although not as potently as crmp2, and that this process is regulated by ser522/ser518/thr514/thr509 phosphorylation in both cases. We demonstrate that cdk5 primes crmp2 and crmp4 for subsequent phosphorylation by gsk3, whereas dyrk2, phosphorylates and primes only crmp4 in vitro	SIGNOR-146011
P23769	Q5D1E8	0	post transcriptional regulation	up-regulates quantity	0.2	Here, we show that Regnase-1 regulates self-renewal of HSPCs through modulating the stability of Gata2 and Tal1 mRNA	SIGNOR-259943
Q96GD4	P54274	1	phosphorylation	up-regulates activity	0.366	Our data indicate that AURKB can phosphorylate the integral telomere DNA-binding Shelterin protein TERF1 at S404 (within the DNA-binding domain) in vitro .	SIGNOR-279440
P38936	O43293	0	phosphorylation	up-regulates quantity by stabilization	0.316	ZIP kinase phosphorylates p21(WAF1) at Thr145 and alanine-substituted mutations in the p21(WAF1) phosphorylation site alter its ability to be phosphorylated by ZIP kinase. \| Transfected ZIPK can promote the phosphorylation of p21(WAF1) at Thr145 in vivo and can increase the half-life of p21(WAF1)	SIGNOR-251085
P58876	Q14493	0	translation regulation	up-regulates quantity by expression	0.2	Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA\|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control.	SIGNOR-265378
P27361	Q01094	1	phosphorylation	up-regulates	0.292	Erk also undergoes rapid translocation into the nucleus, where it phosphorylates and activates a variety of transcription factor targets, including sp1, e2f, elk-1, and ap1	SIGNOR-121991
Q15942	P31749	0	phosphorylation	down-regulates	0.415	Akt binds and phosphorylates zyxin on serine 142, leading to its association with acinus zyxin is a substrate of caspases, but akt phosphorylation fails to protect its proteolytic degradation	SIGNOR-156122
P00390	Q13131	0	phosphorylation	up-regulates activity	0.288	Mechanistically, AMPKα1 regulate the glutathione reductase (GSR) phosphorylation possibly through residue Thr507 which enhances its activity.	SIGNOR-273734
O14920	P54646	0	phosphorylation	up-regulates	0.257	These results demonstrate that the ikk is a direct substrate of ampk_2 and that its phosphorylation on ser177 and ser181no initiates the activation of the ampk_2 in endothelial cells which in turn phosphorylates and activates the _-subunit of the ikk. The latter also induces a higher rate of ikk auto-inactivation and thus attenuates the activation of nf_b and the expression of inflammatory genes	SIGNOR-174405
Q12913	P00533	1	dephosphorylation	up-regulates quantity by stabilization	0.49	We report the identification of PTPRK and PTPRJ (density-enhanced phosphatase-1 [DEP-1]) as EGFR-targeting phosphatases. DEP-1 is a tumor suppressor that dephosphorylates and thereby stabilizes EGFR by hampering its ability to associate with the CBL-GRB2 ubiquitin ligase complex\|By employing commercially available antibodies, which are supposed to recognize specific tyrosine phosphorylation sites of EGFR, we found that depletion of endogenous DEP-1 nonselectively increased receptor phosphorylation, affecting all three sites we analyzed (tyrosines 1045, 1068, and 1173	SIGNOR-248697
P68400	P11831	1	phosphorylation	up-regulates activity	0.552	Casein kinase II (CKII) phosphorylates the mammalian transcription factor serum response factor (SRF) on a serine residue(s) located within a region of the protein spanning amino acids 70 to 92, thereby enhancing its DNA-binding activity in vitro.\| Nevertheless, additional mutation of serines 77 and 79 was required before phosphorylation and enhanced binding were completely abolished. Thus, serines 77 and 79 could also be recognized by CKII if serines 83 and 85 were mutated.	SIGNOR-250955
P22455	P40763	1	phosphorylation	up-regulates activity	0.402	Activation of Stat1 and Stat3 by FGFR derivatives. Lysates of 293T cells transfected as indicated were analysed by Western blotting using Phospho-Stat1 (Y701) antisera (top) or Stat1 antisera (bottom). (b) The same lysates in (a) were re-examined for phosphorylated Stat3 by Western blotting with Phospho-Stat3 (Y705) (top). all three FGFR family members examined here are able to lead to Stat activation. Expression of the 'TDII-like' derivatives of FGFR1, FGFR3, and FGFR4, as well as myrR1-WT, led to phosphorylation of both Stat1 and Stat3.	SIGNOR-251142
Q96GD4	Q12888	1	phosphorylation	up-regulates activity	0.409	Here we report for the first time that tumor suppressor p53-binding protein 1 (53BP1) is phosphorylated at serine 1342 (S1342) by Aurora kinase B both in vitro and in human cells, which is required for optimal recruitment of 53BP1 at kinetochores.	SIGNOR-264411
Q9Y570	P67775	1	demethylation	down-regulates activity	0.905	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-265748
Q9UNN4	P19784	0	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
P04626	P03372	1	phosphorylation	up-regulates	0.572	The results presented here show for the first time that er redistribution to the cytoplasm and its interaction with her2 are important downstream effects of her2 overexpression, that erk1/2 is important for er cytoplasmic localization, and that subcellular localization of er may play a mechanistic role in determining the responsiveness of breast cancer cells to tamoxifen.	SIGNOR-124962
P18031	P51608	0	transcriptional regulation	down-regulates quantity by repression	0.2	In this study, we have demonstrated that the PTPN1 gene, which encodes PTP1B, was a direct target of MECP2 and that PTP1B protein levels were dramatically increased in Mecp2-mutant mice and in fibroblasts derived from patients with RTT.	SIGNOR-264546
Q9Y5T5	P06493	0	phosphorylation	up-regulates	0.455	Here, we report that cyclin-dependent kinase 1 (cdk1) phosphorylates the histone h2a deubiquitinase ubp-m at serine 552 (s552p), and, importantly, this phosphorylation is required for cell cycle progression.	SIGNOR-202678
P49841	Q8NHW3	1	phosphorylation	down-regulates quantity by destabilization	0.257	We also demonstrate that gsk-3 triggers mafa sequential phosphorylation on residues s61, t57, t53, and s49 /we demonstrated that phosphorylation by gsk-3 is conserved among the large maf proteins. It couples ubiquitination/degradation and transcriptional activation and modulates maf biological activity./ Taken together, these results suggest that, in contrast to what can be expected from ubiquitination/degradation, gsk-3-mediated mafa phosphorylation increases its transactivating ability, thereby controlling its biological activity.	SIGNOR-159462
Q9ULV1	Q6UXX9	0	ubiquitination	down-regulates quantity	0.313	Here we show that the cell-surface transmembrane E3 ubiquitin ligase zinc and ring finger 3 (ZNRF3) and its homologue ring finger 43 (RNF43) are negative feedback regulators of Wnt signalling. ZNRF3 is associated with the Wnt receptor complex, and inhibits Wnt signalling by promoting the turnover of frizzled and LRP6.	SIGNOR-260117
O60936	P49840	0	phosphorylation	down-regulates quantity by destabilization	0.2	The present study provided evidence that GSK3alpha and beta directly phosphorylates Arc, resulting in its subsequent degradation.	SIGNOR-279179
Q15139	P22059	1	phosphorylation	down-regulates	0.444	Pkd attenuates the function of both cert and osbp by phosphorylation at their respective ser(132) and ser(240) residues (phosphorylation inhibition)	SIGNOR-171756
P51955	Q68D86	1	phosphorylation	down-regulates activity	0.2	CCDC102B is recruited to the centrosome by C-Nap1 (also known as CEP250) and interacts with the centrosome linker components rootletin and LRRC45. CCDC102B decorates and facilitates the formation of rootletin filaments. Furthermore, CCDC102B is phosphorylated by Nek2A (an isoform encoded by NEK2) and is disassociated from the centrosome at the onset of mitosis.	SIGNOR-275626
Q13627	Q96EB6	1	phosphorylation	up-regulates activity	0.54	DYRK1A and DYRK3 directly phosphorylate SIRT1 at Thr(522), promoting deacetylation of p53.\|DYRK1A and DYRK3 promote cell survival through phosphorylation and activation of SIRT1.	SIGNOR-278473
O43293	Q13464	0	phosphorylation	up-regulates activity	0.306	ROCK1 phosphorylates and activates ZIPK suggesting that at least some of these physiological functions may require both enzymes.	SIGNOR-279102
P62820	O43318	0	phosphorylation	up-regulates activity	0.2	TAK1 preferentially phosphorylates the inactive (GDP-bound) state of Rab1. Phosphorylation of Rab1 disrupts interaction with GDP dissociation inhibitor 1 (GDI1), but not guanine exchange factor (GEF) or GTPase-activating protein (GAP) enzymes, and is exclusive to membrane-localized Rab1, suggesting phosphorylation may stimulate Rab1 membrane association. Furthermore, we found phosphorylation of Rab1 at T75 to be essential for Rab1 function.	SIGNOR-277270
Q9NS91	Q9BXW9	1	ubiquitination	up-regulates activity	0.521	In summary, these findings suggest a model, where Rad18 promotes monoubiquitination of FANCD2, and associates with a functional complex involving Rad51, BRCA2, and FANCD2 in the repair of CPT induced stalled or collapsed forks.\|In this study we focused on the role of Rad18 mediated activation of FANCD2 and its functional relationship with BRCA2 and Rad51 proteins in repair of CPT induced lesions.	SIGNOR-278712
Q00535	O75469	1	phosphorylation	down-regulates activity	0.345	In vitro kinase assays showed that Cdk5 directly phosphorylates PXR.\|Taken together, these data indicate that Cdk5 negatively regulates PXR activity, and that inhibition of Cdk5 is at least partially responsible for flavonoids induced activation of PXR.	SIGNOR-279402
Q99418	P05129	0	phosphorylation	down-regulates activity	0.332	ARNO is phosphorylated in vivo by PKC on a single serine residue, S392, located within the carboxy-terminal polybasic domain. Mutation of S392 to alanine does not prevent ARNO-mediated actin rearrangements, suggesting that phosphorylation does not lead to ARNO activation [6]. Here, we report that phosphorylation negatively regulates ARNO exchange activity through a 'PH domain electrostatic switch'.	SIGNOR-249025
Q9GZU7	Q15672	1	dephosphorylation	down-regulates activity	0.2	These results indicate that SCP1 is the phosphatase that counter-regulates the MAPK-mediated phosphorylation of S68-Twist1.	SIGNOR-245962
P25098	Q16581	1	phosphorylation	down-regulates activity	0.2	These findings indicated that agonist-induced C3aR phosphorylation by GRK2 promotes C3aR desensitization.	SIGNOR-279044
O15530	P11362	0	phosphorylation	up-regulates activity	0.2	Y105 phosphorylation of PKM2, which is involved in FGFR1-regulated PDHK1 expression, appears to be an upstream event that precedes FGFR1-dependent phosphorylation and activation of PDHK1 in cancer cell metabolism.	SIGNOR-279174
P61764	P05129	0	phosphorylation	down-regulates activity	0.386	Munc18a is essential for neurotransmitter release by exocytosis and can be phosphorylated by PKC in vitro on Ser-306 and Ser-313. We demonstrate that it is phosphorylated on Ser-313 in response to phorbol ester treatment in adrenal chromaffin cells. Mutation of both phosphorylation sites to glutamate reduces its affinity for syntaxin and so acts as a phosphomimetic mutation.	SIGNOR-249187
P49841	O60341	1	phosphorylation	up-regulates activity	0.265	GSK3beta phosphorylates KDM1A serine 683 upon priming phosphorylation of KDM1A serine 687 by CK1alpha.\|Together, these results support the notion that GSK3\u03b2 stabilizes KDM1A by decreasing its ubiquitination.	SIGNOR-278225
Q06413	Q9H2X6	0	phosphorylation	down-regulates activity	0.399	HIPK2 associates with the MEF2C\u2013HDAC4 complex and phosphorylates MEF2C.	SIGNOR-279192
P17612	P21333	1	phosphorylation	up-regulates	0.2	Site-directed mutagenesis analysis indicated that serine 2152 is the unique substrate in the c-terminal region of abp for endogenously activated pka.	SIGNOR-126659
P04792	P23443	0	phosphorylation	down-regulates	0.309	Ser-15, ser-78, and ser-82 in hsp27 (ser-15 and ser-86 in hsp25) are part of the rxxs motif, a known recognition site for p70rsk.	SIGNOR-186959
Q00535	O43426	1	phosphorylation	down-regulates activity	0.505	Cdk5 phosphorylation inhibited the inositol 5-phosphatase activity of synaptojanin 1, whereas dephosphorylation by calcineurin stimulated such activity.\|The activity of synaptojanin 1 was also stimulated by its interaction with endophilin 1, its major binding partner at the synapse. Notably, Cdk5 phosphorylated serine 1144, which is adjacent to the endophilin binding site.	SIGNOR-279685
P49459	P50750	0	phosphorylation	up-regulates activity	0.449	CDK9 phosphorylates RNA polymerase II CTD at serine 2 to recruit the RNF20/40 E3 ubiquitin ligase, which is required for H2Bub1, and phosphorylates UBE2A at serine 120 to increase its activity in regulating H2Bub1.	SIGNOR-279025
P13639	O00418	0	phosphorylation	down-regulates	0.788	Ef-2 kinase phosphorylates ef-2 at 3 threonine residues: thr-53, thr-56, thr-58. Phosphorylation of thr56 and thr58 was found to be an ordered process, modification of thr56 preceding, and apparently being required for, phosphorylation of thr58.	SIGNOR-38556
P49336	Q9UHV7	1	phosphorylation	down-regulates quantity by destabilization	0.901	Here, cyclin C-Cdk8 phosphorylation of Med13 most likely primes the phosphodegron for destruction.	SIGNOR-279687
P48729	Q13158	1	phosphorylation	down-regulates activity	0.333	FADD is essential for death receptor (DR)-induced apoptosis.\|Phosphorylation of FADD at serine 194 by CKIalpha regulates its nonapoptotic activities	SIGNOR-139307
P78314	P43405	0	phosphorylation	up-regulates activity	0.552	By using the transient expression system in COS-7 cells, we have demonstrated that 3BP2 was predominantly phosphorylated on Tyr174, Tyr183, and Tyr446 when it was coexpressed with Syk.	SIGNOR-246596
O95863	Q13315	0	phosphorylation	up-regulates activity	0.482	ATM-mediated Snail Serine 100 phosphorylation regulates cellular radiosensitivity.	SIGNOR-279587
Q06830	Q96KB5	0	phosphorylation	up-regulates	0.26	We report that prx1 is newly discovered direct target of topk. Our results demonstrate that topk phosphorylation of prx1 at ser-32 inhibits uvb-induced apoptosis in rpmi7951 melanoma cells by increasing prx1 peroxidase activity and decreasing the intracellular accumulation of h2o2.	SIGNOR-166901
O43623	O96013	0	phosphorylation	up-regulates quantity by stabilization	0.2	P21 activated kinase 4 (PAK4) directly phosphorylates Slug, resulting in pro malignant Slug stabilization.	SIGNOR-280057
Q8IXI2	O60260	0	ubiquitination	down-regulates quantity by destabilization	0.2	We observe that Parkin efficiently ubiquitylates Miro1 at highly conserved lysine residues, 153, 230, 235, 330 and 572, upon phosphorylation by PINK1.	SIGNOR-278561
P31749	P28482	1	phosphorylation	up-regulates activity	0.533	AKT1 stimulated PLD activity via activation of ERK.\|AKT1 actually phosphorylated ERK2 as a substrate (K(m) 1 \u03bcm).	SIGNOR-279136
P45983	Q9Y6W6	0	dephosphorylation	down-regulates	0.705	Mkp-5 directly dephosphorylates sapk/jnk and p38 in vitromkp-5 binds to p38 and sapk/jnk, but not to mapk/erk, and inactivates p38 and sapk/jnk	SIGNOR-68986
P35398	Q8N2Q7	1	transcriptional regulation	up-regulates quantity by expression	0.2	Some genes which are directly regulated by RORA such as NLGN1 and NTRK2 have been shown to be associated with increased susceptibility to ASD (Correia et al. 2010; Ylisaukko-oja et al. 2005).	SIGNOR-265136
P08047	P67775	0	dephosphorylation	up-regulates activity	0.264	These results indicate that the signals from TCDD or OP caused PP2A-mediated dephosphorylation of Sp1 at Ser-59 and induced CYP1A1 transcription	SIGNOR-248223
P49662	P57764	1	cleavage	up-regulates activity	0.647	Co-expression of GSDMD with caspase-1, 4, 5 or 11 but not apoptotic caspases (caspase-2, 8 and 9) in 293T cells induced the same cleavage of GSDMD\|inflammatory caspases specifically cleave GSDMD after the 272FLTD275 (or 273LLSD276) sequence \|	SIGNOR-256417
P60484	P68400	0	phosphorylation	down-regulates activity	0.68	The C-terminal tail of PTEN is also the target of mutations in tumors. As mentioned, this region contains the main phosphorylation sites mapped to residues Ser362, Thr366, Ser370, Ser380, Thr382, Thr383, and Ser385, and the kinases involved are casein kinase 2 (CK2), GSK3_, LKB1, and MAST.84,97-101 The phosphorylation of the tail has been shown to enhance PTEN stability but at the same time decrease its phosphatase activity	SIGNOR-89830
P35568	Q04759	0	phosphorylation	down-regulates activity	0.567	Protein kinase C Theta inhibits insulin signaling by phosphorylating IRS1 at Ser(1101).	SIGNOR-260906
P40424	P42771	1	transcriptional regulation	up-regulates quantity by expression	0.308	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-267239
P35637	P43243	1	relocalization	up-regulates activity	0.486	Moreover, FUS interacts with another nuclear matrix-associated protein Matrin3, which is muted in a subset of familial ALS cases and reportedly interacts with TDP-43. Interestingly, ectopic ALS-linked FUS mutant sequestered endogenous Matrin3 and SAFB1 in the cytoplasmic aggregates.	SIGNOR-262822
Q9UHD2	P06239	0	phosphorylation	down-regulates activity	0.2	The Src family kinases (SFKs) Lck, Hck, and Fgr directly phosphorylate TBK1 at Tyr354/394, to prevent TBK1 dimerization and activation.	SIGNOR-276724
Q9Y397	P01112	1	palmitoylation	up-regulates activity	0.435	Covalent lipid modifications mediate the membrane attachment and biological activity of Ras proteins. All Ras isoforms are farnesylated and carboxyl-methylated at the terminal cysteine; H-Ras and N-Ras are further modified by palmitoylation. Here we report that H- and N-Ras are palmitoylated by a human protein palmitoyltransferase encoded by the ZDHHC9 and GCP16 genes. DHHC9 is an integral membrane protein that contains a DHHC cysteine-rich domain. GCP16 encodes a Golgi-localized membrane protein.	SIGNOR-261352
Q969H0	Q13315	0	phosphorylation	up-regulates activity	0.425	In response to ionizing radiation, ATM phosphorylates FBXW7 at serine 26 to recruit it to DNA double-strand break (DSB) sites, whereas activated DNA-PKcs phosphorylates XRCC4 at serines 325/326, which promotes binding of XRCC4 to FBXW7	SIGNOR-259942
Q13485	Q99717	0	phosphorylation	up-regulates	0.675	Whereas alk5 signalling is mediated by phosphorylation of smad2 and smad3 proteins, alk1 signalling is mediated by smad1, smad5, and smad8. Activated smads form a complex with the common smad (co-smad; smad4 in mammals) and shuttle into the nucleus.	SIGNOR-168737
Q8NEB9	P51149	0	guanine nucleotide exchange factor	up-regulates activity	0.484	The p150 adapter protein is in a complex with rab7. The hVPS34/p150 complex colocalized with rab7 on late endosomes and hVPS34 activity was dependent on nucleotide cycling of rab7	SIGNOR-261302
Q9BZL6	Q9UQL6	1	phosphorylation	up-regulates activity	0.295	Histone deacetylase (HDAC) 5 and 7, two members of the class II of classical HDAC [62], are in vivo substrates of PKD3 and PKD [63]. In response to a variety of signals, including phorbol esters, T cell receptor engagement, vascular endothelial growth factor and angiotensin stimulation, the activity of HDAC5 and 7 are regulated by a mechanism that involves PKD3 and PKD-mediated phosphorylation of the highly conserved Ser259 and Ser498 residues that are located in N-terminus of class II HDACs [63–67].	SIGNOR-275929
Q06830	P06493	0	phosphorylation	down-regulates	0.35	Peroxiredoxin (prx) i is a member of the peroxiredoxin family of peroxidases and contains a consensus site (thr(90)-pro-lys-lys) for phosphorylation by cyclin-dependent kinases (cdks). This protein has now been shown to be phosphorylated specifically on thr(90) by several cdks, including cdc2, in vitro. Phosphorylation of prx i on thr(90) reduced the peroxidase activity of this protein by 80%.	SIGNOR-87097
P50750	O00267	1	phosphorylation	up-regulates	0.776	We describe an evolutionarily conserved repetitive heptapeptide motif (consensus = g-s-r/q-t-p) in the c-terminal region (ctr) of hspt5, which, like the c-terminal domain (ctd) of rna pol ii, is highly phosphorylated by p-tefb. Thr-4 residues of the ctr repeats are functionally important phosphorylation sites. In vitro, thr-4 phosphorylation is critical for the elongation activation activity of dsif	SIGNOR-143939
Q07955	P78362	0	phosphorylation	up-regulates activity	0.616	In contrast, SRPK1 or SRPK2 overexpression upregulated the phosphorylation and nucleus accumulation of SRSF1.\|Therefore, SRPK1 and SRPK2 may directly phosphorylate SRSF1 and promote it nucleus translocation, subsequently modulate MKNK2 alternative splicing.	SIGNOR-279660
P68400	P46060	1	phosphorylation	up-regulates	0.31	Phosphorylation of rangap1 stabilizes its interaction with ran and ranbp1. Serine-358 (358s) was identified as the major phosphorylation site. Experiments using purified recombinant kinase and specific inhibitors such as drb and apigenin strongly suggest that casein kinase ii (ck2) is the responsible kinase	SIGNOR-143948
P11309	Q15796	1	phosphorylation	up-regulates activity	0.2	We further showed that PIM1 could interact with and phosphorylate Smad2 or Smad3 in the nucleus to induce transcription factor (ZEB1, ZEB2, Snail1, Snail2 and Twist) expression and EMT.	SIGNOR-279090
Q9H2X6	Q9P1Z0	1	phosphorylation	down-regulates activity	0.379	The human protein kinase HIPK2 phosphorylates and downregulates the methyl-binding transcription factor ZBTB4.	SIGNOR-262882
P09619	P19174	1	phosphorylation	up-regulates	0.859	Tyrosine phosphorylation has been shown to increase the enzymatic activity of plc-? / we show that the human pdgf ?- And ?-Receptors differ quantitatively in their abilities to associate with and phosphorylate plc-? And to stimulate inositol phosphate production.	SIGNOR-28179
Q12778	P35558	1	transcriptional regulation	up-regulates quantity by expression	0.428	Phosphorylated foxo1 is inactive and retained in the cytosol. Mkp-3 mediated dephosphorylation activates foxo1 and subsequentially promotes its nuclear translocation and binding to the promoters of gluconeogenic genes, such as phosphoenolpyruvate carboxykinase (pepck) and glucose-6-phosphatase (g6pase).	SIGNOR-197200
P17481	Q01995	1	transcriptional regulation	down-regulates quantity by repression	0.2	Results from these experiments demonstrated that in 10T1/2 cells Hoxa10-1 increased the activity of the telokin promoter 3-fold without affecting the activity of the other promoters analyzed (Fig. 2A). Similar results were also observed in A10 SMC (data not shown). In contrast, Hoxb8 significantly repressed the activity of the telokin, smooth muscle α-actin, and SM22α promoters by 70, 50, and 70%, respectively	SIGNOR-261642
Q13705	Q15796	1	phosphorylation	up-regulates activity	0.776	It has been suggested that binding of myostatin to the ActRIIB results in the phosphorylation of two serine residues of Smad2 or Smad3 at COOH domains	SIGNOR-254984
Q13131	P11908	1	phosphorylation	down-regulates activity	0.2	We demonstrate here that glucose deprivation or hypoxia results in the AMPK-mediated phosphorylation of phosphoribosyl pyrophosphate synthetase 1 (PRPS1) S180 and PRPS2 S183, leading to conversion of PRPS hexamers to monomers and thereby inhibiting PRPS1/2 activity, nucleotide synthesis, and nicotinamide adenine dinucleotide (NAD) production.	SIGNOR-265731
P61586	P15311	1	phosphorylation	up-regulates activity	0.76	Rev-erbα interacted with OPHN-1, promoted RhoA activity and phosphorylation of ERM. etection of phosphorylated ezrin (Thr567)/radixin (Thr564)/moesin (Thr558)(p-ERM) in Rev-erbαfl/flCre− and Rev-erbαfl/flPF4Cre+ platelets using phospho-specific antibodies.	SIGNOR-268429
O75385	O75592	0	ubiquitination	down-regulates quantity	0.284	Cell-based results demonstrate that the human PHR protein PAM restricts ULK1 protein levels (Fig.\u00a05h, i), and is sufficient to ubiquitinate ULK1 in a proteasome-dependent manner (Fig.\u00a05j).\|Human PAM ubiquitinates ULK1 and regulates ULK1 levels.	SIGNOR-278765
P33981	Q00987	1	phosphorylation	up-regulates activity	0.264	(D and E) MDM2 was phosphorylated by hMps1 at Thr4, Thr306 and Ser307 in vitro.\|In support, the MDM2 Ser307 to Ala mutant was less stable than the wild-type protein when coexpressed with hMps1 (Supplementary Figure S2B and C). hMps1 promotes MDM2-mediated H2B ubiquitination. (A) wild-type but not kinase-dead mutant hMps1 promotes MDM2-mediated H2B ubiquitination. 293T cells were transfected with the indicated plasmids and lysates were prepared for the Ni-NTA bead pulldown assay. 46999999="S307A"}	SIGNOR-279315
Q8TEB7	P52566	1	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
Q13237	P29350	1	phosphorylation	up-regulates activity	0.2	PKGII directly phosphorylated and stimulated SHP-1 activity	SIGNOR-276288

P57764

P51878

0

cleavage

up-regulates activity

0.62

Co-expression of GSDMD with caspase-1, 4, 5 or 11 but not apoptotic caspases (caspase-2, 8 and 9) in 293T cells induced the same cleavage of GSDMD|inflammatory caspases specifically cleave GSDMD after the 272FLTD275 (or 273LLSD276) sequence |

SIGNOR-256418

Q99942

P49023

1

ubiquitination

down-regulates quantity

0.407

Here we demonstrate that the human homologue of RNF5 associates with the amino-terminal domain of paxillin, resulting in its ubiquitination. RNF5 requires intact RING and C-terminal domains to mediate paxillin ubiquitination. Concomitantly, RNF5 expression results in inhibition of cell motility. Via targeting of paxillin ubiquitination, which alters its localization, RNF5 emerges as a novel regulator of cell motility.

SIGNOR-271479

O15111

Q9BUZ4

1

phosphorylation

down-regulates

0.384

Traf4 is atypical within its family because it is the only traf family member to negatively regulate innate immune signaling. Ikk_'s phosphorylation of serine-426 on traf4 was required for this negative regulation.

SIGNOR-197253

Q13546

P21580

0

ubiquitination

down-regulates quantity

0.655

The amino-terminal domain of A20, which is a de-ubiquitinating (DUB) enzyme of the OTU (ovarian tumour) family, removes lysine-63 (K63)-linked ubiquitin chains from receptor interacting protein (RIP), an essential mediator of the proximal TNF receptor 1 (TNFR1) signalling complex. The carboxy-terminal domain of A20, composed of seven C2/C2 zinc fingers, then functions as a ubiquitin ligase by polyubiquitinating RIP with K48-linked ubiquitin chains, thereby targeting RIP for proteasomal degradation.

SIGNOR-259978

P06493

Q13501

1

phosphorylation

up-regulates

0.343

Here we show that cdk1 phosphorylates p62 in vitro and in vivo at t269 and s272, which is necessary for the maintenance of appropriate cyclin b1 levels and the levels of cdk1 activity necessary to allow cells to properly enter and exit mitosis.

SIGNOR-169012

Q13224

Q00535

0

phosphorylation

down-regulates quantity

0.443

Cdk5 phosphorylates NR2B at Ser1116 and controls surface level expression.|Reduction in Cdk5 activity, as well as disruption of Cdk5-NR2B interactions consistently increased NR2B surface levels and facilitated NMDA mediated synaptic function.

SIGNOR-278265

O00429

Q9GZY8

0

relocalization

up-regulates activity

0.601

Mff functions as an essential factor in mitochondrial recruitment of Drp1.

SIGNOR-245957

P78362

Q9UKV3

1

phosphorylation

up-regulates

0.476

Here, we show that srpk2 binds and phosphorylates acinus, an sr protein essential for rna splicing, and redistributes it from the nuclear speckles to the nucleoplasm, resulting in cyclin a1 but not a2 up-regulation. Acinus s422d, an srpk2 phosphorylation mimetic, enhances cyclin a1 transcription, whereas acinus s422a, an unphosphorylatable mutant, blocks the stimulatory effect of srpk2

SIGNOR-179006

O60566

Q12834

1

phosphorylation

up-regulates activity

0.993

Furthermore, BUBR1 phosphorylates p55CDC in vitro, and the phosphorylation of p55CDC by BUBR1 appears to be correlated with spindle checkpoint activation.

SIGNOR-279507

Q04760

P22607

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-276181

P04637

P49841

0

phosphorylation

up-regulates activity

0.728

Glycogen synthase kinase3 beta phosphorylates serine 33 of p53 and activates p53's transcriptional activity.

SIGNOR-251258

Q96PU5

Q9C0H2

1

polyubiquitination

down-regulates quantity by destabilization

0.2

Our data indicate that Nedd4-2 binds to two family members, TTYH2 and TTYH3, which contain consensus PY ((L/P)PXY) binding sites for HECT type E3 ubiquitin ligases, but not to TTYH1, which lacks this motif. Consistently, Nedd4-2 ubiquitinates both TTYH2 and TTYH3. Importantly, we have shown that endogenous TTYH2 and Nedd4-2 are binding partners and demonstrated that the TTYH2 PY motif is essential for these interactions. We have also shown that Nedd4-2-mediated ubiquitination of TTYH2 is a critical regulator of cell surface and total cellular levels of this protein.

SIGNOR-272633

Q14674

O60216

1

cleavage

down-regulates quantity by destabilization

0.78

In order to segregate sister chromatids to opposite poles in anaphase, cohesin has to be removed from chromosomes. In budding yeast, the prevalent mode of cohesin removal is by proteolytic cleavage of the Scc1 subunit at the onset of anaphase by the endopeptidase separase

SIGNOR-275537

O96013

P28698

1

phosphorylation

up-regulates activity

0.2

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

SIGNOR-277422

Q13501

Q9Y4E8

0

deubiquitination

down-regulates activity

0.26

SQSTM1 Is a Substrate for RNF26 and the DUB USP15. Catalytically competent RNF26 (light red) recruits SQSTM1 (blue) and mediates ubiquitin ligation (red), which serves to attract UBDs of specific vesicle-associated adaptors. Dissociation of the RNF26/SQSTM1 complex, promoted by the DUB USP15 (yellow), releases target vesicles for (4) fast transport into the cell periphery.

SIGNOR-269829

P10415

Q15173

0

dephosphorylation

down-regulates

0.323

Pp2a directly interacts with the bh4 domain of bcl2 as a docking site to potentially bridge pp2a to bcl2's flexible loop domain containing the target serine 70 phosphorylation site.

SIGNOR-181559

Q05655

P62714

0

dephosphorylation

down-regulates activity

0.3

PP2A(c) displayed the highest specific activity towards PKCdelta. The role of PP2A(c) in the dephosphorylation of PKCdelta in cells was supported by the demonstration that these proteins could be co-immunoprecipitated from NIH3T3 cells.|In conclusion, the evidence here indicates that PKCdelta de-phosphorylation and hence inactivation is effected by PP2A with which it forms a complex

SIGNOR-248595

Q15831

Q15418

0

phosphorylation

down-regulates activity

0.288

Negative regulation of the LKB1/AMPK pathway by ERK in human acute myeloid leukemia cellsBRAFV600E activates downstream molecules, including ERK and p90 ribosomal S6 kinase (RSK), and leads to the phosphorylation of LKB-1 at Ser428 by these kinases. This cascade results in the dissociation of LKB1 from AMPK.

SIGNOR-209871

O14641

Q96GF1

0

polyubiquitination

down-regulates quantity by destabilization

0.466

The E3 ligase RNF185 negatively regulates osteogenic differentiation by targeting Dvl2 for degradation. Overexpression of RNF185 decreases the exogenous and endogenous level of Dvl2, promotes the ubiquitination and degradation of Dvl2

SIGNOR-272173

Q8N2H9

Q15306

1

ubiquitination

down-regulates activity

0.2

Peli3 induces the degradation of IRF4 through K48‐mediated ubiquitination |To detect the direct interaction of Peli3 and IRF4, Peli3 and IRF4 DNA constructs were transfected into HEK293 cells.

SIGNOR-280453

Q05519

P02649

1

post transcriptional regulation

up-regulates quantity by stabilization

0.2

We demonstrate that SFRS11 directly binds to the 3' UTR of LRP8 mRNA, as well as to the third exon of apoE mRNA, resulting in stabilization of these mRNAs, eventually deactivating JNK signaling.

SIGNOR-269671

P01111

P49842

0

phosphorylation

up-regulates activity

0.306

STK19 Phosphorylates NRAS Protein at Serine 89|STK19 phosphorylates NRAS to enhance its binding to its downstream effectors and promotes oncogenic NRAS-mediated melanocyte malignant transformation.|

SIGNOR-264566

Q14195

P49841

0

phosphorylation

up-regulates activity

0.475

Together, these results suggest that crmp4 is able to increase neurite formation and elongation in neurons, although not as potently as crmp2, and that this process is regulated by ser522/ser518/thr514/thr509 phosphorylation in both cases. We demonstrate that cdk5 primes crmp2 and crmp4 for subsequent phosphorylation by gsk3, whereas dyrk2, phosphorylates and primes only crmp4 in vitro

SIGNOR-146011

P23769

Q5D1E8

0

post transcriptional regulation

up-regulates quantity

0.2

Here, we show that Regnase-1 regulates self-renewal of HSPCs through modulating the stability of Gata2 and Tal1 mRNA

SIGNOR-259943

Q96GD4

P54274

1

phosphorylation

up-regulates activity

0.366

Our data indicate that AURKB can phosphorylate the integral telomere DNA-binding Shelterin protein TERF1 at S404 (within the DNA-binding domain) in vitro .

SIGNOR-279440

P38936

O43293

0

phosphorylation

up-regulates quantity by stabilization

0.316

ZIP kinase phosphorylates p21(WAF1) at Thr145 and alanine-substituted mutations in the p21(WAF1) phosphorylation site alter its ability to be phosphorylated by ZIP kinase. | Transfected ZIPK can promote the phosphorylation of p21(WAF1) at Thr145 in vivo and can increase the half-life of p21(WAF1)

SIGNOR-251085

P58876

Q14493

0

translation regulation

up-regulates quantity by expression

0.2

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

SIGNOR-265378

P27361

Q01094

1

phosphorylation

up-regulates

0.292

Erk also undergoes rapid translocation into the nucleus, where it phosphorylates and activates a variety of transcription factor targets, including sp1, e2f, elk-1, and ap1

SIGNOR-121991

Q15942

P31749

0

phosphorylation

down-regulates

0.415

Akt binds and phosphorylates zyxin on serine 142, leading to its association with acinus zyxin is a substrate of caspases, but akt phosphorylation fails to protect its proteolytic degradation

SIGNOR-156122

P00390

Q13131

0

phosphorylation

up-regulates activity

0.288

Mechanistically, AMPKα1 regulate the glutathione reductase (GSR) phosphorylation possibly through residue Thr507 which enhances its activity.

SIGNOR-273734

O14920

P54646

0

phosphorylation

up-regulates

0.257

These results demonstrate that the ikk is a direct substrate of ampk_2 and that its phosphorylation on ser177 and ser181no initiates the activation of the ampk_2 in endothelial cells which in turn phosphorylates and activates the _-subunit of the ikk. The latter also induces a higher rate of ikk auto-inactivation and thus attenuates the activation of nf_b and the expression of inflammatory genes

SIGNOR-174405

Q12913

P00533

1

dephosphorylation

up-regulates quantity by stabilization

0.49

We report the identification of PTPRK and PTPRJ (density-enhanced phosphatase-1 [DEP-1]) as EGFR-targeting phosphatases. DEP-1 is a tumor suppressor that dephosphorylates and thereby stabilizes EGFR by hampering its ability to associate with the CBL-GRB2 ubiquitin ligase complex|By employing commercially available antibodies, which are supposed to recognize specific tyrosine phosphorylation sites of EGFR, we found that depletion of endogenous DEP-1 nonselectively increased receptor phosphorylation, affecting all three sites we analyzed (tyrosines 1045, 1068, and 1173

SIGNOR-248697

P68400

P11831

1

phosphorylation

up-regulates activity

0.552

Casein kinase II (CKII) phosphorylates the mammalian transcription factor serum response factor (SRF) on a serine residue(s) located within a region of the protein spanning amino acids 70 to 92, thereby enhancing its DNA-binding activity in vitro.| Nevertheless, additional mutation of serines 77 and 79 was required before phosphorylation and enhanced binding were completely abolished. Thus, serines 77 and 79 could also be recognized by CKII if serines 83 and 85 were mutated.

SIGNOR-250955

P22455

P40763

1

phosphorylation

up-regulates activity

0.402

Activation of Stat1 and Stat3 by FGFR derivatives. Lysates of 293T cells transfected as indicated were analysed by Western blotting using Phospho-Stat1 (Y701) antisera (top) or Stat1 antisera (bottom). (b) The same lysates in (a) were re-examined for phosphorylated Stat3 by Western blotting with Phospho-Stat3 (Y705) (top). all three FGFR family members examined here are able to lead to Stat activation. Expression of the 'TDII-like' derivatives of FGFR1, FGFR3, and FGFR4, as well as myrR1-WT, led to phosphorylation of both Stat1 and Stat3.

SIGNOR-251142

Q96GD4

Q12888

1

phosphorylation

up-regulates activity

0.409

Here we report for the first time that tumor suppressor p53-binding protein 1 (53BP1) is phosphorylated at serine 1342 (S1342) by Aurora kinase B both in vitro and in human cells, which is required for optimal recruitment of 53BP1 at kinetochores.

SIGNOR-264411

Q9Y570

P67775

1

demethylation

down-regulates activity

0.905

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-265748

Q9UNN4

P19784

0

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

P04626

P03372

1

phosphorylation

up-regulates

0.572

The results presented here show for the first time that er redistribution to the cytoplasm and its interaction with her2 are important downstream effects of her2 overexpression, that erk1/2 is important for er cytoplasmic localization, and that subcellular localization of er may play a mechanistic role in determining the responsiveness of breast cancer cells to tamoxifen.

SIGNOR-124962

P18031

P51608

0

transcriptional regulation

down-regulates quantity by repression

0.2

In this study, we have demonstrated that the PTPN1 gene, which encodes PTP1B, was a direct target of MECP2 and that PTP1B protein levels were dramatically increased in Mecp2-mutant mice and in fibroblasts derived from patients with RTT.

SIGNOR-264546

Q9Y5T5

P06493

0

phosphorylation

up-regulates

0.455

Here, we report that cyclin-dependent kinase 1 (cdk1) phosphorylates the histone h2a deubiquitinase ubp-m at serine 552 (s552p), and, importantly, this phosphorylation is required for cell cycle progression.

SIGNOR-202678

P49841

Q8NHW3

1

phosphorylation

down-regulates quantity by destabilization

0.257

We also demonstrate that gsk-3 triggers mafa sequential phosphorylation on residues s61, t57, t53, and s49 /we demonstrated that phosphorylation by gsk-3 is conserved among the large maf proteins. It couples ubiquitination/degradation and transcriptional activation and modulates maf biological activity./ Taken together, these results suggest that, in contrast to what can be expected from ubiquitination/degradation, gsk-3-mediated mafa phosphorylation increases its transactivating ability, thereby controlling its biological activity.

SIGNOR-159462

Q9ULV1

Q6UXX9

0

ubiquitination

down-regulates quantity

0.313

Here we show that the cell-surface transmembrane E3 ubiquitin ligase zinc and ring finger 3 (ZNRF3) and its homologue ring finger 43 (RNF43) are negative feedback regulators of Wnt signalling. ZNRF3 is associated with the Wnt receptor complex, and inhibits Wnt signalling by promoting the turnover of frizzled and LRP6.

SIGNOR-260117

O60936

P49840

0

phosphorylation

down-regulates quantity by destabilization

0.2

The present study provided evidence that GSK3alpha and beta directly phosphorylates Arc, resulting in its subsequent degradation.

SIGNOR-279179

Q15139

P22059

1

phosphorylation

down-regulates

0.444

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

SIGNOR-171756

P51955

Q68D86

1

phosphorylation

down-regulates activity

0.2

CCDC102B is recruited to the centrosome by C-Nap1 (also known as CEP250) and interacts with the centrosome linker components rootletin and LRRC45. CCDC102B decorates and facilitates the formation of rootletin filaments. Furthermore, CCDC102B is phosphorylated by Nek2A (an isoform encoded by NEK2) and is disassociated from the centrosome at the onset of mitosis.

SIGNOR-275626

Q13627

Q96EB6

1

phosphorylation

up-regulates activity

0.54

DYRK1A and DYRK3 directly phosphorylate SIRT1 at Thr(522), promoting deacetylation of p53.|DYRK1A and DYRK3 promote cell survival through phosphorylation and activation of SIRT1.

SIGNOR-278473

O43293

Q13464

0

phosphorylation

up-regulates activity

0.306

ROCK1 phosphorylates and activates ZIPK suggesting that at least some of these physiological functions may require both enzymes.

SIGNOR-279102

P62820

O43318

0

phosphorylation

up-regulates activity

0.2

TAK1 preferentially phosphorylates the inactive (GDP-bound) state of Rab1. Phosphorylation of Rab1 disrupts interaction with GDP dissociation inhibitor 1 (GDI1), but not guanine exchange factor (GEF) or GTPase-activating protein (GAP) enzymes, and is exclusive to membrane-localized Rab1, suggesting phosphorylation may stimulate Rab1 membrane association. Furthermore, we found phosphorylation of Rab1 at T75 to be essential for Rab1 function.

SIGNOR-277270

Q9NS91

Q9BXW9

1

ubiquitination

up-regulates activity

0.521

In summary, these findings suggest a model, where Rad18 promotes monoubiquitination of FANCD2, and associates with a functional complex involving Rad51, BRCA2, and FANCD2 in the repair of CPT induced stalled or collapsed forks.|In this study we focused on the role of Rad18 mediated activation of FANCD2 and its functional relationship with BRCA2 and Rad51 proteins in repair of CPT induced lesions.

SIGNOR-278712

Q00535

O75469

1

phosphorylation

down-regulates activity

0.345

In vitro kinase assays showed that Cdk5 directly phosphorylates PXR.|Taken together, these data indicate that Cdk5 negatively regulates PXR activity, and that inhibition of Cdk5 is at least partially responsible for flavonoids induced activation of PXR.

SIGNOR-279402

Q99418

P05129

0

phosphorylation

down-regulates activity

0.332

ARNO is phosphorylated in vivo by PKC on a single serine residue, S392, located within the carboxy-terminal polybasic domain. Mutation of S392 to alanine does not prevent ARNO-mediated actin rearrangements, suggesting that phosphorylation does not lead to ARNO activation [6]. Here, we report that phosphorylation negatively regulates ARNO exchange activity through a 'PH domain electrostatic switch'.

SIGNOR-249025

Q9GZU7

Q15672

1

dephosphorylation

down-regulates activity

0.2

These results indicate that SCP1 is the phosphatase that counter-regulates the MAPK-mediated phosphorylation of S68-Twist1.

SIGNOR-245962

P25098

Q16581

1

phosphorylation

down-regulates activity

0.2

These findings indicated that agonist-induced C3aR phosphorylation by GRK2 promotes C3aR desensitization.

SIGNOR-279044

O15530

P11362

0

phosphorylation

up-regulates activity

0.2

Y105 phosphorylation of PKM2, which is involved in FGFR1-regulated PDHK1 expression, appears to be an upstream event that precedes FGFR1-dependent phosphorylation and activation of PDHK1 in cancer cell metabolism.

SIGNOR-279174

P61764

P05129

0

phosphorylation

down-regulates activity

0.386

Munc18a is essential for neurotransmitter release by exocytosis and can be phosphorylated by PKC in vitro on Ser-306 and Ser-313. We demonstrate that it is phosphorylated on Ser-313 in response to phorbol ester treatment in adrenal chromaffin cells. Mutation of both phosphorylation sites to glutamate reduces its affinity for syntaxin and so acts as a phosphomimetic mutation.

SIGNOR-249187

P49841

O60341

1

phosphorylation

up-regulates activity

0.265

GSK3beta phosphorylates KDM1A serine 683 upon priming phosphorylation of KDM1A serine 687 by CK1alpha.|Together, these results support the notion that GSK3\u03b2 stabilizes KDM1A by decreasing its ubiquitination.

SIGNOR-278225

Q06413

Q9H2X6

0

phosphorylation

down-regulates activity

0.399

HIPK2 associates with the MEF2C\u2013HDAC4 complex and phosphorylates MEF2C.

SIGNOR-279192

P17612

P21333

1

phosphorylation

up-regulates

0.2

Site-directed mutagenesis analysis indicated that serine 2152 is the unique substrate in the c-terminal region of abp for endogenously activated pka.

SIGNOR-126659

P04792

P23443

0

phosphorylation

down-regulates

0.309

Ser-15, ser-78, and ser-82 in hsp27 (ser-15 and ser-86 in hsp25) are part of the rxxs motif, a known recognition site for p70rsk.

SIGNOR-186959

Q00535

O43426

1

phosphorylation

down-regulates activity

0.505

Cdk5 phosphorylation inhibited the inositol 5-phosphatase activity of synaptojanin 1, whereas dephosphorylation by calcineurin stimulated such activity.|The activity of synaptojanin 1 was also stimulated by its interaction with endophilin 1, its major binding partner at the synapse. Notably, Cdk5 phosphorylated serine 1144, which is adjacent to the endophilin binding site.

SIGNOR-279685

P49459

P50750

0

phosphorylation

up-regulates activity

0.449

CDK9 phosphorylates RNA polymerase II CTD at serine 2 to recruit the RNF20/40 E3 ubiquitin ligase, which is required for H2Bub1, and phosphorylates UBE2A at serine 120 to increase its activity in regulating H2Bub1.

SIGNOR-279025

P13639

O00418

0

phosphorylation

down-regulates

0.788

Ef-2 kinase phosphorylates ef-2 at 3 threonine residues: thr-53, thr-56, thr-58. Phosphorylation of thr56 and thr58 was found to be an ordered process, modification of thr56 preceding, and apparently being required for, phosphorylation of thr58.

SIGNOR-38556

P49336

Q9UHV7

1

phosphorylation

down-regulates quantity by destabilization

0.901

Here, cyclin C-Cdk8 phosphorylation of Med13 most likely primes the phosphodegron for destruction.

SIGNOR-279687

P48729

Q13158

1

phosphorylation

down-regulates activity

0.333

FADD is essential for death receptor (DR)-induced apoptosis.|Phosphorylation of FADD at serine 194 by CKIalpha regulates its nonapoptotic activities

SIGNOR-139307

P78314

P43405

0

phosphorylation

up-regulates activity

0.552

By using the transient expression system in COS-7 cells, we have demonstrated that 3BP2 was predominantly phosphorylated on Tyr174, Tyr183, and Tyr446 when it was coexpressed with Syk.

SIGNOR-246596

O95863

Q13315

0

phosphorylation

up-regulates activity

0.482

ATM-mediated Snail Serine 100 phosphorylation regulates cellular radiosensitivity.

SIGNOR-279587

Q06830

Q96KB5

0

phosphorylation

up-regulates

0.26

We report that prx1 is newly discovered direct target of topk. Our results demonstrate that topk phosphorylation of prx1 at ser-32 inhibits uvb-induced apoptosis in rpmi7951 melanoma cells by increasing prx1 peroxidase activity and decreasing the intracellular accumulation of h2o2.

SIGNOR-166901

O43623

O96013

0

phosphorylation

up-regulates quantity by stabilization

0.2

P21 activated kinase 4 (PAK4) directly phosphorylates Slug, resulting in pro malignant Slug stabilization.

SIGNOR-280057

Q8IXI2

O60260

0

ubiquitination

down-regulates quantity by destabilization

0.2

We observe that Parkin efficiently ubiquitylates Miro1 at highly conserved lysine residues, 153, 230, 235, 330 and 572, upon phosphorylation by PINK1.

SIGNOR-278561

P31749

P28482

1

phosphorylation

up-regulates activity

0.533

AKT1 stimulated PLD activity via activation of ERK.|AKT1 actually phosphorylated ERK2 as a substrate (K(m) 1 \u03bcm).

SIGNOR-279136

P45983

Q9Y6W6

0

dephosphorylation

down-regulates

0.705

Mkp-5 directly dephosphorylates sapk/jnk and p38 in vitromkp-5 binds to p38 and sapk/jnk, but not to mapk/erk, and inactivates p38 and sapk/jnk

SIGNOR-68986

P35398

Q8N2Q7

1

transcriptional regulation

up-regulates quantity by expression

0.2

Some genes which are directly regulated by RORA such as NLGN1 and NTRK2 have been shown to be associated with increased susceptibility to ASD (Correia et al. 2010; Ylisaukko-oja et al. 2005).

SIGNOR-265136

P08047

P67775

0

dephosphorylation

up-regulates activity

0.264

These results indicate that the signals from TCDD or OP caused PP2A-mediated dephosphorylation of Sp1 at Ser-59 and induced CYP1A1 transcription

SIGNOR-248223

P49662

P57764

1

cleavage

up-regulates activity

0.647

Co-expression of GSDMD with caspase-1, 4, 5 or 11 but not apoptotic caspases (caspase-2, 8 and 9) in 293T cells induced the same cleavage of GSDMD|inflammatory caspases specifically cleave GSDMD after the 272FLTD275 (or 273LLSD276) sequence |

SIGNOR-256417

P60484

P68400

0

phosphorylation

down-regulates activity

0.68

The C-terminal tail of PTEN is also the target of mutations in tumors. As mentioned, this region contains the main phosphorylation sites mapped to residues Ser362, Thr366, Ser370, Ser380, Thr382, Thr383, and Ser385, and the kinases involved are casein kinase 2 (CK2), GSK3_, LKB1, and MAST.84,97-101 The phosphorylation of the tail has been shown to enhance PTEN stability but at the same time decrease its phosphatase activity

SIGNOR-89830

P35568

Q04759

0

phosphorylation

down-regulates activity

0.567

Protein kinase C Theta inhibits insulin signaling by phosphorylating IRS1 at Ser(1101).

SIGNOR-260906

P40424

P42771

1

transcriptional regulation

up-regulates quantity by expression

0.308

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-267239

P35637

P43243

1

relocalization

up-regulates activity

0.486

Moreover, FUS interacts with another nuclear matrix-associated protein Matrin3, which is muted in a subset of familial ALS cases and reportedly interacts with TDP-43. Interestingly, ectopic ALS-linked FUS mutant sequestered endogenous Matrin3 and SAFB1 in the cytoplasmic aggregates.

SIGNOR-262822

Q9UHD2

P06239

0

phosphorylation

down-regulates activity

0.2

The Src family kinases (SFKs) Lck, Hck, and Fgr directly phosphorylate TBK1 at Tyr354/394, to prevent TBK1 dimerization and activation.

SIGNOR-276724

Q9Y397

P01112

1

palmitoylation

up-regulates activity

0.435

Covalent lipid modifications mediate the membrane attachment and biological activity of Ras proteins. All Ras isoforms are farnesylated and carboxyl-methylated at the terminal cysteine; H-Ras and N-Ras are further modified by palmitoylation. Here we report that H- and N-Ras are palmitoylated by a human protein palmitoyltransferase encoded by the ZDHHC9 and GCP16 genes. DHHC9 is an integral membrane protein that contains a DHHC cysteine-rich domain. GCP16 encodes a Golgi-localized membrane protein.

SIGNOR-261352

Q969H0

Q13315

0

phosphorylation

up-regulates activity

0.425

In response to ionizing radiation, ATM phosphorylates FBXW7 at serine 26 to recruit it to DNA double-strand break (DSB) sites, whereas activated DNA-PKcs phosphorylates XRCC4 at serines 325/326, which promotes binding of XRCC4 to FBXW7

SIGNOR-259942

Q13485

Q99717

0

phosphorylation

up-regulates

0.675

Whereas alk5 signalling is mediated by phosphorylation of smad2 and smad3 proteins, alk1 signalling is mediated by smad1, smad5, and smad8. Activated smads form a complex with the common smad (co-smad; smad4 in mammals) and shuttle into the nucleus.

SIGNOR-168737

Q8NEB9

P51149

0

guanine nucleotide exchange factor

up-regulates activity

0.484

The p150 adapter protein is in a complex with rab7. The hVPS34/p150 complex colocalized with rab7 on late endosomes and hVPS34 activity was dependent on nucleotide cycling of rab7

SIGNOR-261302

Q9BZL6

Q9UQL6

1

phosphorylation

up-regulates activity

0.295

Histone deacetylase (HDAC) 5 and 7, two members of the class II of classical HDAC [62], are in vivo substrates of PKD3 and PKD [63]. In response to a variety of signals, including phorbol esters, T cell receptor engagement, vascular endothelial growth factor and angiotensin stimulation, the activity of HDAC5 and 7 are regulated by a mechanism that involves PKD3 and PKD-mediated phosphorylation of the highly conserved Ser259 and Ser498 residues that are located in N-terminus of class II HDACs [63–67].

SIGNOR-275929

Q06830

P06493

0

phosphorylation

down-regulates

0.35

Peroxiredoxin (prx) i is a member of the peroxiredoxin family of peroxidases and contains a consensus site (thr(90)-pro-lys-lys) for phosphorylation by cyclin-dependent kinases (cdks). This protein has now been shown to be phosphorylated specifically on thr(90) by several cdks, including cdc2, in vitro. Phosphorylation of prx i on thr(90) reduced the peroxidase activity of this protein by 80%.

SIGNOR-87097

P50750

O00267

1

phosphorylation

up-regulates

0.776

We describe an evolutionarily conserved repetitive heptapeptide motif (consensus = g-s-r/q-t-p) in the c-terminal region (ctr) of hspt5, which, like the c-terminal domain (ctd) of rna pol ii, is highly phosphorylated by p-tefb. Thr-4 residues of the ctr repeats are functionally important phosphorylation sites. In vitro, thr-4 phosphorylation is critical for the elongation activation activity of dsif

SIGNOR-143939

Q07955

P78362

0

phosphorylation

up-regulates activity

0.616

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

SIGNOR-279660

P68400

P46060

1

phosphorylation

up-regulates

0.31

Phosphorylation of rangap1 stabilizes its interaction with ran and ranbp1. Serine-358 (358s) was identified as the major phosphorylation site. Experiments using purified recombinant kinase and specific inhibitors such as drb and apigenin strongly suggest that casein kinase ii (ck2) is the responsible kinase

SIGNOR-143948

P11309

Q15796

1

phosphorylation

up-regulates activity

0.2

We further showed that PIM1 could interact with and phosphorylate Smad2 or Smad3 in the nucleus to induce transcription factor (ZEB1, ZEB2, Snail1, Snail2 and Twist) expression and EMT.

SIGNOR-279090

Q9H2X6

Q9P1Z0

1

phosphorylation

down-regulates activity

0.379

The human protein kinase HIPK2 phosphorylates and downregulates the methyl-binding transcription factor ZBTB4.

SIGNOR-262882

P09619

P19174

1

phosphorylation

up-regulates

0.859

Tyrosine phosphorylation has been shown to increase the enzymatic activity of plc-? / we show that the human pdgf ?- And ?-Receptors differ quantitatively in their abilities to associate with and phosphorylate plc-? And to stimulate inositol phosphate production.

SIGNOR-28179

Q12778

P35558

1

transcriptional regulation

up-regulates quantity by expression

0.428

Phosphorylated foxo1 is inactive and retained in the cytosol. Mkp-3 mediated dephosphorylation activates foxo1 and subsequentially promotes its nuclear translocation and binding to the promoters of gluconeogenic genes, such as phosphoenolpyruvate carboxykinase (pepck) and glucose-6-phosphatase (g6pase).

SIGNOR-197200

P17481

Q01995

1

transcriptional regulation

down-regulates quantity by repression

0.2

Results from these experiments demonstrated that in 10T1/2 cells Hoxa10-1 increased the activity of the telokin promoter 3-fold without affecting the activity of the other promoters analyzed (Fig. 2A). Similar results were also observed in A10 SMC (data not shown). In contrast, Hoxb8 significantly repressed the activity of the telokin, smooth muscle α-actin, and SM22α promoters by 70, 50, and 70%, respectively

SIGNOR-261642

Q13705

Q15796

1

phosphorylation

up-regulates activity

0.776

It has been suggested that binding of myostatin to the ActRIIB results in the phosphorylation of two serine residues of Smad2 or Smad3 at COOH domains

SIGNOR-254984

Q13131

P11908

1

phosphorylation

down-regulates activity

0.2

We demonstrate here that glucose deprivation or hypoxia results in the AMPK-mediated phosphorylation of phosphoribosyl pyrophosphate synthetase 1 (PRPS1) S180 and PRPS2 S183, leading to conversion of PRPS hexamers to monomers and thereby inhibiting PRPS1/2 activity, nucleotide synthesis, and nicotinamide adenine dinucleotide (NAD) production.

SIGNOR-265731

P61586

P15311

1

phosphorylation

up-regulates activity

0.76

Rev-erbα interacted with OPHN-1, promoted RhoA activity and phosphorylation of ERM. etection of phosphorylated ezrin (Thr567)/radixin (Thr564)/moesin (Thr558)(p-ERM) in Rev-erbαfl/flCre− and Rev-erbαfl/flPF4Cre+ platelets using phospho-specific antibodies.

SIGNOR-268429

O75385

O75592

0

ubiquitination

down-regulates quantity

0.284

Cell-based results demonstrate that the human PHR protein PAM restricts ULK1 protein levels (Fig.\u00a05h, i), and is sufficient to ubiquitinate ULK1 in a proteasome-dependent manner (Fig.\u00a05j).|Human PAM ubiquitinates ULK1 and regulates ULK1 levels.

SIGNOR-278765

P33981

Q00987

1

phosphorylation

up-regulates activity

0.264

(D and E) MDM2 was phosphorylated by hMps1 at Thr4, Thr306 and Ser307 in vitro.|In support, the MDM2 Ser307 to Ala mutant was less stable than the wild-type protein when coexpressed with hMps1 (Supplementary Figure S2B and C). hMps1 promotes MDM2-mediated H2B ubiquitination. (A) wild-type but not kinase-dead mutant hMps1 promotes MDM2-mediated H2B ubiquitination. 293T cells were transfected with the indicated plasmids and lysates were prepared for the Ni-NTA bead pulldown assay. 46999999="S307A"}

SIGNOR-279315

Q8TEB7

P52566

1

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

Q13237

P29350

1

phosphorylation

up-regulates activity

0.2

PKGII directly phosphorylated and stimulated SHP-1 activity

SIGNOR-276288