GleghornLab/Signor_3class · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	labels int64 0 2	mechanism stringclasses 40 values	effect stringclasses 10 values	score float64 0.1 0.99 ⌀	sentence stringlengths 10 1.63k ⌀	signor_id stringlengths 12 14
P17481	P40426	2	binding	up-regulates activity	0.484	the ability of HoxB8 to heterodimerizes with endogenous Pbx proteins on DNA alters gene transcription in a manner that prevents progression through an intrinsic genetic differentiation program. In conjunction with Pbx, HoxB8 could alter transcription of Pbx target genes by direct or indirect mechanisms.	SIGNOR-223149
Q15011	Q8IUR6	0	transcriptional regulation	up-regulates quantity by expression	0.2	Luman/CREB3 induces transcription of the endoplasmic reticulum (ER) stress response protein Herp through an ER stress response element.	SIGNOR-261575
Q92570	P04637	0	transcriptional regulation	up-regulates quantity by expression	0.264	We showed that p53 directly bound the promoter of NR4A3 gene and induced its transcription. p53 transactivates the NR4A3 promoter in H1299 cells.	SIGNOR-256200
Q92686	P17252	0	phosphorylation	up-regulates activity	0.394	Phosphorylation of RC3 by PKC alpha, beta, or gamma was stimulated by Ca2+, phospholipid, and diacylglycerol. A single site, Ser36, which is adjacent to the predicted calmodulin (CaM)-binding domain, was phosphorylated by these enzymes. Phosphorylation of RC3 by PKC or PKM, a protease-degraded PKC, was inhibited by CaM. The effect of CaM apparently targets at RC3, as phosphorylation of protamine sulfate by PKM was not inhibited by CaM.	SIGNOR-248913
P31751	Q86YS7	1	phosphorylation	up-regulates activity	0.513	MS analysis of an HA-CDP138 sample from the in vitro kinase assay revealed that active Akt2 induces CDP138 phosphorylation at serine (Ser)197, which lies within a consensus Akt substrate motif RQRLIS 197 ( xref ).	SIGNOR-279585
P25490	P07948	0	phosphorylation	down-regulates activity	0.2	In the case of Lyn overexpression, single mutations at either tyrosine 8, 254, or 383 severely reduced Lyn-mediated YY1 phosphorylation, suggesting that these three sites may be targets of Lyn in vivo (Fig. 3, A and B).	SIGNOR-276930
Q9Y2X7	P12931	0	phosphorylation	up-regulates activity	0.542	Tyrosines 246 and 293 are required to hold GIT1 in a closed conformation.Hyperphosphorylation of GIT1-N by Src and pervanadate does not affect its binding in vitro to full length GIT1 proteins. Mutations Y246E and Y293E of GIT1 enhance binding to paxillin.	SIGNOR-276627
P04233	P14174	2	binding	up-regulates	0.735	Mif binds to the extracellular domain of cd74, and cd74 is required for mif-induced activation of the extracellular signal-regulated kinase-1/2 map kinase cascade, cell proliferation, and pge2 production.	SIGNOR-101526
P31994	P07948	0	phosphorylation	up-regulates activity	0.43	Therefore, we conclude that FcgammaRIIb1 phosphorylation upon BCR-FcgammaR coligation is most likely due to BCR-associated Lyn	SIGNOR-249380
Q5JTC6	O15169	1	relocalization	up-regulates activity	0.789	Amer1 binds ck1gamma, recruits axin and gsk3beta to the plasma membrane and promotes complex formation between axin and lrp6.	SIGNOR-171886
Q00535	P50406	1	phosphorylation	down-regulates activity	0.374	Cdk5 phosphorylates the 5-HT6R on serine 350 (Ser350)\|This suggests that the 5-HT6R is unable to interact with GPRIN1 when it is phosphorylated by Cdk5.	SIGNOR-264407
Q9GZQ4	P50148	2	binding	up-regulates activity	0.464	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257218
O60716	P48729	0	phosphorylation	up-regulates activity	0.2	Moreover, CK1α phosphorylates p120-catenin on Ser268 and Ser269, releasing this protein from the signalosome and facilitating the subsequent phosphorylation of cadherin and the disruption of this cadherin interaction with LRP5/6	SIGNOR-277893
P20807	P20810	2	binding	down-regulates activity	0.569	In addition to Ca2+, calpastatin has a key role in the regulation of calpain. Calpastatin, a heat-stable protein ranging from ~70 to ~140 kDa of apparent molecular weight depending on the cell type, is considered a specific endogenous inhibitor of calpains\|The calpastatin molecule contains four inhibitory units [75–77]. Each of these units binds to one calpain molecule [75–77]. Therefore, the ratio calpain/calpastatin plays a key role in the regulation of calpain activity [78–80]. The inhibitory effect of calpastatin requires Ca2+-dependent high-affinity binding to three sites of calpain	SIGNOR-251603
Q15418	P16220	1	phosphorylation	up-regulates activity	0.747	The rsks phosphorylate the trascription factor creb at serine 133 to promote cell survival.	SIGNOR-72117
P23276	P14138	1	cleavage	up-regulates activity	0.676	These data demonstrate that the Kell blood group protein is a proteolytic enzyme that processes big ET-3, generating ET-3, a potent bioactive peptide with multiple biological roles.	SIGNOR-256354
P45983	Q14934	1	phosphorylation	up-regulates activity	0.467	Here, we showed that the nuclear factor of activated T3 (NFAT3) is phosphorylated by JNK1 or JNK2 at Ser(213) and Ser(217), which are located in the conserved SP motif.\|Moreover, a 3xNFAT-luc reporter gene assay indicated that NFAT3 transcriptional activity was increased in a dose dependent manner by JNK1 or JNK2.	SIGNOR-280033
P20823	Q9NPD5	1	transcriptional regulation	up-regulates quantity by expression	0.251	Farnesoid X receptor, hepatocyte nuclear factors 1alpha and 3beta are essential for transcriptional activation of the liver-specific organic anion transporter-2 gene.\|This study demonstrated that the transcription of the LST-2 gene is regulated by three transcription factors, FXR, HNF1alpha, and HNF3beta.	SIGNOR-268988
P09874	P49959	1	relocalization	up-regulates activity	0.2	PARP1 collaborates with Mre11 to promote replication fork restart after release from replication blocks, most likely by recruiting Mre11 to the replication fork to promote resection of DNA.	SIGNOR-272478
Q99967	P28482	0	phosphorylation	up-regulates activity	0.454	CITED2 coactivation is enhanced by activation of MAPK1 and requires T166.\|CITED2 is phosphorylated by MAPK1 at S85, T166 and T175.	SIGNOR-278410
P46108	P22681	2	binding	up-regulates	0.824	These results indicate that crk binds to c-cbl in a tyrosine phosphorylation-dependent manner.	SIGNOR-39241
P38606	P25490	0	transcriptional regulation	up-regulates quantity by expression	0.325	We investigated the relationship between transcription factor YY1 and ATP6V1A, and found that mRNA expression of YY1 had significant correlation with that of ATP6V1A. To validate that YY1 transcriptionally regulates ATP6V1A, we discovered that the ATP6V1A core promoter region contains three YY1 binding sites. Moreover, RNAi-mediated knockdown of YY1 in GC cells significantly decreased ATP6V1A mRNA and protein expression, while YY1 overexpression increased ATP6V1A expression level.	SIGNOR-260635
P27361	Q15366	1	phosphorylation	up-regulates quantity by stabilization	0.323	We also identified 4 hnRNP-E2 MAPKERK1/2 phosphorylation sites and demonstrated that hnRNP-E2 is a bona fide MAPKERK1/2 substrate and that MAPKERK1/2-dependent phosphorylation of hnRNP-E2 at these amino acid residues is essential for increased hnRNP-E2 expression in BCR/ABL-expressing cells. Serine/threonine to alanine substitution abolishes hnRNP-E2 phosphorylation and markedly decreases its stability in BCR/ABL-expressing myeloid precursors. Consistent with the existence of a BCR/ABL-MAPK pathway that posttranslationally regulates hnRNP-E2 expression, sequence analysis of hnRNP-E2 revealed the presence of 4 consensus ERK phosphorylation sites (S/T-P)35,36 at amino acid residues 173, 189, 213, and 272 (Figure 2B).	SIGNOR-262916
Q96BA8	Q96BA8	2	binding	up-regulates activity	0.2	E4BP4, ATF-6, OASIS, and XBP-1 all formed strong homodimeric associations on the array Transcription factor dimerization can increase the selectivity of protein-DNA interactions and generate a large amount of DNA binding diversity from a relatively small number of proteins	SIGNOR-224205
P26012	O14713	2	binding	down-regulates activity	0.313	Integrins also bind to many PTBdomain-containing proteins (Calderwood et al., 2003) – including Dok1 and integrincytoplasmic-domain-associated protein 1 (ICAP1) – and these can compete with talin for binding to integrin and so can impair activation	SIGNOR-257667
P53701	P99999	1	chemical modification	up-regulates activity	0.44	Cytochrome c oxidase catalyzes the reduction of molecular oxygen to water, a process in which four electrons, four protons, and one molecule of oxygen are consumed. The reaction is coupled to the pumping of four additional protons across the membrane. According to the currently accepted concept, the pumping of all four protons occurs after the binding of oxygen to the reduced enzyme and is exclusively coupled to the last two electron transfer steps.	SIGNOR-280296
Q92918	P00519	0	phosphorylation	up-regulates activity	0.379	C-Abl phosphorylates HPK1 in cytoplasm and stimulates HPK1 activity. the c-Abl phosphorylation site (YXXP) in HPK1 (Y232QPP; aa 232–235) is localized in HPK1-KD	SIGNOR-251429
Q14457	P46934	0	ubiquitination	up-regulates quantity by stabilization	0.46	BECN1 stability was increased by NEDD4 via K6 and K27 ubiquitination during autophagy induction, thereby promoting autophagy activation.\|Further, NEDD4 mediated K6- and K27- linkage ubiquitination of BECN1, leading to elevated stability of BECN1 and increased autophagy.	SIGNOR-278558
P00519	P46527	1	phosphorylation	down-regulates quantity	0.595	A conserved tyrosine residue (Y88) in the Cdk-binding domain of p27 can be phosphorylated by the Src-family kinase Lyn and the oncogene product BCR-ABL	SIGNOR-245293
Q13153	P53667	1	phosphorylation	up-regulates activity	0.614	Activation of lim-kinase by pak1 couplesp21-activated kinase (pak1) phosphorylates lim-kinase at threonine residue 508 within lim-kinase's activation loop	SIGNOR-72142
O94761	Q7L590	2	binding	down-regulates	0.509	Mcm10 inhibits recq4 helicase activity.	SIGNOR-187701
Q96TA1	P01112	2	binding	up-regulates activity	0.2	EGFR phosphorylates FAM129B, resulting in binding of phosphorylated FAM129B to H-Ras and reduced the association of p120-RasGAP with H-Ras, thereby enhancing H-Ras activation for ERK1/2-dependent β-catenin transactivation for enhanced Warburg effect, tumor cell proliferation, and brain tumorigenesis.	SIGNOR-273659
P62837	Q9UPQ7	2	binding	up-regulates activity	0.385	Our initial tests of various E2s showed that the RING domain of PDZRN3 exhibits ubiquitin ligase activity in the presence of E1 and the UbcH5 family of E2 enzymes (Fig. 3 A). Consistent with this finding, GST pull-down assays showed that PDZRN3 directly interacts with the UbcH5B ubiquitin conjugating enzyme (Fig. 3 B).	SIGNOR-271663
P12931	P10301	1	phosphorylation	down-regulates activity	0.58	The small gtpase, r-ras, affects cell adhesion by maintaining integrin activity. Activated src oncogene phosphorylates r-ras and suppresses integrin activity. the src phosphorylation site in r-ras was tyrosine 66	SIGNOR-111189
Q9UNE7	Q15797	1	ubiquitination	down-regulates	0.328	These results suggest that chip can interact with the smad1/smad4 proteins and block bmp signal transduction through the ubiquitin-mediated degradation of smad proteins.	SIGNOR-120731
Q86U86	Q13049	0	ubiquitination	down-regulates quantity by destabilization	0.2	TRIM32 ubiquitination of PB1 leads to its protein degradation.	SIGNOR-278735
Q969Q1	P61088	0	ubiquitination	up-regulates activity	0.539	We used MuRF1 as the E3 as it functions with all these E2s to ubiquitinate one of its typical substrates, troponin I Although UbcH1 and UbcH13/Uev1a support ubiquitination of troponin I by MuRF1, these E2s do not support ubiquitination of S5a, unlike Class I E2s.	SIGNOR-272737
P31751	P03372	1	phosphorylation	up-regulates activity	0.509	AKT activate ERalpha in the absence of estrogen. The consensus AKT phosphorylation site Ser-167 of ERalpha is required for phosphorylation and activation by AKT.	SIGNOR-251490
P30047	P30793	2	binding	down-regulates activity	0.864	The enzyme activity of GTP cyclohydrolase I is controlled by a regulatory protein for this enzyme, GFRP, which is a pentamer of identical subunits. GFRP mediates feedback inhibition of GTP cyclohydrolase I activity by BH4, and the inhibition by BH4 is reversed by phenylalanine	SIGNOR-252203
Q15643	P10827	2	binding	up-regulates	0.387	Trip230 binds to rb independently of thyroid hormone while it forms a complex with tr in a thyroid hormone-dependent manner. Ectopic expression of the protein trip230 in cells, but not a mutant form that does not bind to tr, enhances specifically tr-dependent transcriptional activity.	SIGNOR-50348
Q13885	Q14980	2	binding	up-regulates	0.2	Direct binding of numa to tubulin is mediated by a novel sequence motif in the tail domain that bundles and stabilizes microtubules.	SIGNOR-116936
Q8NER1	P29350	0	dephosphorylation	down-regulates activity	0.2	Shp-1 dephosphorylates TRPV1 in dorsal root ganglion neurons and alleviates CFA-induced inflammatory pain in rats.\|These results suggested that Shp-1 dephosphorylated and inhibited TRPV1 in DRG neurons, contributing to maintain thermal nociceptive thresholds in normal rats, and as a compensatory mechanism, Shp-1 increased in DRGs of rats with CFA-induced inflammatory pain, which was involved in protecting against excessive thermal hyperalgesia.	SIGNOR-277129
P48431	P31749	0	phosphorylation	up-regulates quantity by stabilization	0.532	In contrast, phosphorylation of Sox2 by AKT1 at T118 blocks K119me by Set7 and stabilizes Sox2.	SIGNOR-279003
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
O14795	Q86UR5	0	relocalization	up-regulates activity	0.798	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-264385
Q15796	Q96PU5	0	ubiquitination	down-regulates activity	0.781	Through its ww domain, nedd4l specifically recognizes a tgf-beta-induced phosphothr-protyr motif in the linker region, resulting in smad2/3 polyubiquitination and degradation	SIGNOR-217622
Q15637	P18146	2	binding	up-regulates activity	0.295	GNRH1 induces expression of early growth response 1 (EGR1), which interacts with steroidogenic factor 1 (SF1) and paired-like homeodomain transcription factor 1 (PITX1) to regulate Lhb promoter activity.	SIGNOR-254914
Q96KG9	P31749	0	phosphorylation	up-regulates activity	0.255	In previous work, we demonstrated that TEIF (transcriptional element-interacting factor) distributes in the centrosomes and regulates centrosome status under both physiologic and pathologic conditions.\|A consensus motif for Akt phosphorylation (RHRVLT) proved to be involved in centrosomal TEIF localization, and the 469-threonine of this motif may be phosphorylated by Akt both in vitro and in vivo. Elimination of this phosphorylated site on TEIF caused reduced centrosome distribution and centrosome splitting or amplification.	SIGNOR-265496
Q86UT6	Q9Y4K3	2	binding	down-regulates activity	0.472	Immunoprecipitation experiments showed that NLRX1 interacted with TRAF6 and TRAF3, but not with TRAF2 or TRAF5. These results further suggest that NLRX1 specifically inhibits TLR-induced TRAF6-dependent NF-kB signaling through targeting TRAF6.	SIGNOR-260364
Q99759	Q13501	1	phosphorylation	up-regulates activity	0.556	MEKK3 overexpression, but not that of a kinase dead mutant, was able to induce the phosphorylation of p62 at T269 and S272 (XREF_FIG), which correlated with mTORC1 activation (XREF_FIG), suggesting that MEKK3 could be a bona fide regulator of p62 phosphorylation and mTORC1 activity.	SIGNOR-279532
O14733	Q9UQF2	2	binding	up-regulates	0.722	Both jip1 and jip2 selectively bind the mapkk isoform mkk7.	SIGNOR-70848
P07951	P48736	0	phosphorylation	up-regulates activity	0.335	Here, we demonstrate a requirement for the protein kinase activity of PI(3)K in agonist-dependent beta-adrenergic receptor (betaAR) internalization. Using PI(3)K mutants with either protein or lipid phosphorylation activity, we identify the cytoskeletal protein non-muscle tropomyosin as a substrate of PI(3)K, which is phosphorylated in a wortmannin-sensitive manner on residue Ser 61. A constitutively dephosphorylated (S61A) tropomyosin mutant blocks agonist-dependent betaAR internalization, whereas a tropomyosin mutant that mimics constitutive phosphorylation (S61D) complements the PI(3)K mutant, with only lipid phosphorylation activity reversing the defective betaAR internalization.	SIGNOR-263028
P00533	O14939	1	phosphorylation	up-regulates activity	0.516	Using transiently transfected human embryonic kidney fibroblasts (HEK293), we demonstrate here that PLD1 activity, and to a lesser extent PLD2 activity, is stimulated in response to epidermal growth factor (EGF). PLD2, but not PLD1, associates with the EGF receptor in a ligand-independent manner and becomes tyrosine-phosphorylated upon EGF receptor activation. Tyrosine 11 (Tyr-11) of PLD2 was identified as the specific phosphorylation site. Mutation of this residue to phenylalanine enhanced basal activity almost 2-fold	SIGNOR-251095
O43597	Q9BUB5	0	phosphorylation	down-regulates	0.531	The spry2/nedd4 association involves the ww domains of nedd4 and requires phosphorylation of the mnk2 kinase sites, ser(112) and ser(121), on spry2. mnk2 silencing decreased spry2-nedd4 interactions and also augmented the ability of spry2 to inhibit fibroblast growth factor signaling. endogenous and overexpressed nedd4 polyubiquitinate spry2 via lys(48) on ubiquitin and decrease its stability.	SIGNOR-188889
O43683	Q12834	1	phosphorylation	down-regulates activity	0.992	Bub1 directly phosphorylates Cdc20 in vitro and inhibits the ubiquitin ligase activity of APC/C(Cdc20) catalytically. A Cdc20 mutant with all six Bub1 phosphorylation sites removed is refractory to Bub1-mediated phosphorylation and inhibition in vitro.	SIGNOR-250606
P18887	P68400	0	phosphorylation	up-regulates	0.395	Xrcc1 phosphorylation by ck2 is required for its stability and efficient dna repair	SIGNOR-165419
Q00535	Q8NEB9	1	phosphorylation	down-regulates	0.357	Thr159 phosphorylation negatively regulates the ptdins3 kinase activity of vps34 and autophagy cdk5/p25, a neuronal cdk shown to play a role in alzheimer's disease, can also phosphorylate thr159 of vps34.	SIGNOR-165772
Q16549	P30305	1	phosphorylation	down-regulates	0.2	We propose that regulation of cdc25b phosphorylation by p38 is a critical event for initiating the g2/m checkpoint after ultraviolet radiation	SIGNOR-107423
Q96L34	Q15831	0	phosphorylation	up-regulates	0.535	Lkb1 is a master kinase that activates 13 kinases of the ampk subfamily, including mark/par-1we recently demonstrated that the lkb1 tumour suppressor kinase, in complex with the pseudokinase strad and the scaffolding protein mo25, phosphorylates and activates amp-activated protein kinase (ampk). A total of 12 human kinases (nuak1, nuak2, brsk1, brsk2, qik, qsk, sik, mark1, mark2, mark3, mark4 and melk) are related to ampk. Here we demonstrate that lkb1 can phosphorylate the t-loop of all the members of this subfamily, apart from melk, increasing their activity >50-fold	SIGNOR-122682
O96017	Q15717	1	phosphorylation	down-regulates activity	0.55	Given the fact that Chk2 phosphorylates HuR at residues S88, S100 and T118 and that each individual phosphorylation site by Chk2 plays a distinct role in regulating HuR- binding to different target mRNAs (22,42), we further tested HuR mutants with alanine substitutions at each of the Chk2 phosphorylation sites.	SIGNOR-278163
P26447	P35579	2	binding	down-regulates activity	0.418	Our results show that S100A4 regulates cell polarization during directed motility by affecting the localization of protrusions through interactions with myosin-IIA, with S100A4 expressing cells displaying few side protrusions and extensive forward protrusions during chemotaxis compared with control cells. The mechanisms by which these antibodies and S100A4 increase protrusive activity and promote cellular motility are not well understood, but the observation that S100A4 can inhibit the actin-activated ATPase of myosin-IIA (34) suggests that S100A4 could function as a myosin-IIA inhibitor in vivo.	SIGNOR-269282
Q9UKV5	P04114	1	ubiquitination	down-regulates quantity by destabilization	0.29	In physiological condition, the unnecessary apoB is usually ubiquitinated by E3 ligase AMFR, and subsequently degraded by ubiquitination proteasomes.	SIGNOR-278685
Q00987	Q9UN86	2	binding	down-regulates activity	0.3	G3BP2 binds to MDM2 and decreases its E3 ligase activity. The G3BP2 isoform additionally associated with murine double minute 2 (MDM2), a negative regulator of p53. G3BP2 expression resulted in significant reduction in MDM2-mediated p53 ubiquitylation and degradation.	SIGNOR-278892
P49137	P50549	1	phosphorylation	up-regulates	0.612	Neverthless, some transcription factors, such as e47, er81, srf and creb are also phosphorylated by mk2	SIGNOR-166625
P49674	O15534	1	phosphorylation	down-regulates quantity by destabilization	0.842	We show here that mPer proteins, negative limbs of the autoregulatory loop, are specific substrates for CKIepsilon and CKIdelta. The CKI phosphorylation of mPer1 and mPer3 proteins results in their rapid degradation, which is dependent on the ubiquitin-proteasome pathway.	SIGNOR-267997
P49459	P24941	0	phosphorylation	up-regulates	0.374	Hhr6a is phosphorylated in vitro by cdk-1 and -2 on ser120, a residue conserved in all hhr6a homologues, resulting in a 4-fold increase in its ubiquitin-conjugating activity.	SIGNOR-116508
O94782	Q9BXW9	1	deubiquitination	down-regulates activity	0.761	The deubiquitinating enzyme USP1 controls the cellular levels of the DNA damage response protein Ub-FANCD2\|The level of monoubiquitinated FANCD2 protein increases in response to various types of DNA damage in mammalian cells	SIGNOR-263273
Q13144	P05198	1	guanine nucleotide exchange factor	up-regulates activity	0.84	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-269123
P17612	P13612	1	phosphorylation	up-regulates activity	0.494	PKA phosphorylationin vitro blocks the binding of the alpha4 tail to paxillin. A mutation that mimics alpha4 phosphorylation disrupts paxillin binding and promotes cell spreading	SIGNOR-110119
P08754	P31391	2	binding	up-regulates activity	0.45	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-256823
P61586	O94989	0	guanine nucleotide exchange factor	up-regulates activity	0.571	We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)\|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs\| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).	SIGNOR-260540
Q96EP1	P09874	1	polyubiquitination	down-regulates quantity by destabilization	0.427	Here, we show that checkpoint with Forkhead-associated (FHA) and RING finger domain protein (CHFR), an E3 ubiquitin ligase, is recruited to DSBs by poly(ADP-ribose) (PAR). Moreover, CHFR ubiquitinates PAR polymerase 1 (PARP1) and regulates chromatin-associated PARP1 in vivo. Moreover, the poly-ubiquitin chain on PARP1 could be recognized by both anti-K48 and K63-linked poly-ubiquitin chain antibodies, suggesting that CHFR mediates a mixed poly-ubiquitin chain linkage on PARP1. With MG132 treatment, ubiquitinated PARP1 was significantly accumulated (Figure 4D), suggesting that the ubiquitination of PARP1 is likely involved in protein degradation. Consistently, we found that following DNA damage, PARP1 quickly dissociated from the chromatin in the wild-type cells (Figure 4F). However, in the Chfr−/− cells, the dissociation of PARP1 from the chromatin was significantly delayed.	SIGNOR-271470
P22681	P29376	0	phosphorylation	up-regulates	0.369	Although c-cbl is found to be phosphorylated by ltk and therefore is a second candidate linking ltk with the pi3-kinase pathway along with irs-1, we found that the p85 subunit of pi3 kinase directly binds to tyrosine 753 of ltk, which is located within a yxxm motif, a consensus binding amino acid sequence for the sh2 domain of p85.	SIGNOR-49528
P01106	P30279	1	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
O15182	Q15154	0	relocalization	up-regulates	0.297	Rna silencing of pcm-1 leads to reduced assembly of centrin, pericentrin, and ninein at the centrosome	SIGNOR-95016
Q99835	P59768	2	binding	up-regulates	0.385	Consistent with its predicted topology, smo couples to a specific family of inhibitory g protein (gis) to regulate hh signaling.	SIGNOR-199183
P78356	Q16539	0	phosphorylation	down-regulates	0.2	Inhibition of pip4kbeta activity occurs through the direct phosphorylation of pip4kbeta at ser326 by the p38 stress-activated protein kinase.	SIGNOR-149359
P24941	P98177	1	phosphorylation	down-regulates	0.518	Additionally, ck1, dyrk1a, and cdk2 also phosphorylate foxos at various sites to inhibit foxos activity	SIGNOR-183655
Q92547	Q13535	2	binding	up-regulates activity	0.814	These results establish that TopBP1 can activate both Xenopus and human ATR. Furthermore, these experiments provide conclusive evidence that the kinase activity that is induced by TopBP1 is intrinsic to the ATR protein itself and is not due to a kinase that associates with ATR.	SIGNOR-263232
P42345	O75385	1	phosphorylation	down-regulates activity	0.849	mTORC1, which is often referred to as the gatekeeper to autophagy, is a key regulator of the Ulk1-Atg13-FIP200 kinase complex.11,14,25 Under nutrient-rich conditions, active mTORC1 associates with and inactivates the Ulk1-Atg13-FIP200 complex by phosphorylating Ulk1 and Atg13.	SIGNOR-183903
P11308	P04628	1	transcriptional regulation	up-regulates quantity by expression	0.2	Interestingly, our data showed that ERG drastically induced Wnt ligand gene expression.	SIGNOR-261597
P31994	Q86YJ5	0	ubiquitination	down-regulates quantity by destabilization	0.2	MARCH9, a member of the RING-CH family of transmembrane E3 ubiquitin ligases, down-regulates CD4, major histocompatibility complex-I (MHC), and ICAM-1 in lymphoid cells. To identify novel MARCH9 substrates, we used high throughput flow cytometry and quantitative mass spectrometry by stable isotope labeling by amino acids in cell culture (SILAC) to determine the differential expression of plasma membrane proteins in a MARCH9-expressing B cell line. This combined approach identified 13 potential new MARCH9 targets.	SIGNOR-271541
P62834	O95398	0	guanine nucleotide exchange factor	up-regulates activity	0.71	Epac1 (cAMP-GEFI) and Epac2 (cAMP-GEFII) are closely related guanine nucleotide exchange factors (GEFs) for the small GTPase Rap1, which are directly regulated by cAMP. Here we show that both GEFs efficiently activate Rap2 as well.	SIGNOR-263956
Q8IW41	P47712	1	phosphorylation	up-regulates activity	0.334	The p38-activated protein kinases MNK1, MSK1, and PRAK1 phosphorylate cPLA2 in vitro uniquely on Ser-727. By using Chinese hamster ovary, HeLa, and HEK293 cells stably transfected with wild type and phosphorylation site mutant forms of cPLA2, we show that phosphorylation of cPLA2 at both Ser-505 and Ser-727 and elevation of Ca(2+) leads to its activation in agonist-stimulated cells.	SIGNOR-250162
P38398	Q9H4M3	2	binding	down-regulates quantity by destabilization	0.369	The F-box protein FBXO44 mediates BRCA1 ubiquitination and degradation. The Skp1-Cul1-F-box-protein44 (SCF(FBXO44)) complex ubiquitinates full-length BRCA1 in vitro.	SIGNOR-272037
Q14344	Q9HC97	2	binding	up-regulates activity	0.2	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257283
P78527	Q14653	1	phosphorylation	up-regulates	0.43	Phosphorylation of irf-3 by dna-pk after virus infection results in its nuclear retention and delayed proteolysis	SIGNOR-115331
O15033	Q9NR28	1	ubiquitination	down-regulates quantity by destabilization	0.377	AREL1 ubiquitinated SMAC, primarily on Lys62 and Lys191 \|E701A substitution in the AREL1 HECT domain substantially increased its autopolyubiquitination and SMAC ubiquitination activity, whereas deletion of the last three amino acids at the C terminus completely abrogated AREL1 autoubiquitination and reduced SMAC ubiquitination.	SIGNOR-267672
Q96RI1	Q05513	0	phosphorylation	up-regulates	0.38	The effect of fic1 on fxr phosphorylation and nuclear localization and its effects on bsep promoter activity could be blocked with protein kinase c zeta (pkc zeta) inhibitors (pseudosubstrate or small interfering rna silencing). Recombinant pkc zeta directly phosphorylated immunoprecipitated fxr. The mutation of threonine 442 of fxr to alanine yielded a dominant negative protein,	SIGNOR-179771
P28482	Q86U44	1	phosphorylation	up-regulates quantity by stabilization	0.273	Mass spectrometry analysis showed that ERK phosphorylates METTL3 at three highly conserved residues: S43, S50, and S525 (Figures 2D and 2E). Mutational analysis further confirmed these three sites as main ERK phosphorylation sites (Figure 2F). Phosphorylation of METTL3 increases interaction with USP5, decreasing ubiquitination to stabilize the m6 A methyltransferase complex.	SIGNOR-265948
P06241	Q9NWQ8	1	phosphorylation	up-regulates activity	0.703	Thus, Fyn mediates Csk-binding protein-Csk interaction and recruits Csk to rafts by phosphorylating Csk-binding protein.	SIGNOR-279987
Q96PZ7	P84022	2	binding	up-regulates activity	0.2	CSMD1 co-immunoprecipitated with SMAD3, confirming our results that CSMD1 interacts with Smad3 in A375 cells. CSMD1 interacts with Smad3 and induces phosphorylation (p-Smad3). Phosphorylated Smad3 promotes Smad2 phosphorylation and Smad2/3/4 complex formation.	SIGNOR-265151
P42224	P40763	0	transcriptional regulation	up-regulates quantity by expression	0.615	In summary, we report in this study that STAT1 expression is upregulated by nuclear EGFR, EGFRvIII and HER2, and that STAT3 synergizes with the three receptors to further enhance STAT1 expression. These novel findings establish a novel link between the mitogenic ErbB signaling pathway and the inflammatory pathway mediated by STAT1. The oncogenic transcription factor STAT3 binds to the STAT1 promoter and synergizes with nuclear EGFR to significantly enhance STAT1 gene expression.	SIGNOR-263650
Q6UXZ4	P43146	2	binding	down-regulates activity	0.584	In the presence of netrin-1, UNC5 co-immuno-precipitates with DCC, suggesting the formation of a ternary complex of netrin-1 with ecto-domains of DCC and UNC5. DCC binding to netrin-1 alone leads to axon attraction. Importantly, DCC has the ability to switch the netrin-1-mediated responses from attraction to repulsion when another receptor UNC5 co-exists. DCC binding to netrin-1 alone leads to axon attraction. Importantly, DCC has the ability to switch the netrin-1-mediated responses from attraction to repulsion when another receptor UNC5 co-exists.	SIGNOR-268167
Q12955	Q92823	0	relocalization	up-regulates quantity	0.721	Neurofascin, L1, NrCAM, NgCAM, and neuroglian are membrane-spanning cell adhesion molecules with conserved cytoplasmic domains that are believed to play important roles in development of the nervous system. This report presents biochemical evidence that the cytoplasmic domains of these molecules associate directly with ankyrins, a family of spectrin-binding proteins located on the cytoplasmic surface of specialized plasma membrane domains.	SIGNOR-266720
Q12923	P12931	1	dephosphorylation	down-regulates activity	0.54	Mechanistically, RIL suppresses Src activation through interacting with Src and PTPL1, allowing PTPL1 dependent dephosphorylation of Src at the activation loop.\|Our results reveal a novel Src inactivation cycle in which reversion-induced LIM preferentially recognizes active Src and facilitates PTPL1-mediated inactivation of Src.	SIGNOR-277125
Q13144	P49840	0	phosphorylation	down-regulates activity	0.368	We identify multiple phosphorylation sites in the largest, catalytic, subunit (epsilon) of mammalian eIF2B. Glycogen synthase kinase 3 (GSK3) is responsible for phosphorylating Ser535. This regulatory phosphorylation event requires both the fourth site (Ser539) and a distal region, which acts to recruit GSK3 to eIF2Bepsilon in vivo. eIF2Bϵ from mammals or insects is a substrate for glycogen synthase kinase 3 (GSK3), and this inhibits the activity of eIF2B	SIGNOR-251215
O60260	Q8IXI1	1	polyubiquitination	down-regulates quantity by destabilization	0.2	PINK1 phosphorylates Miro, a component of the primary motor/adaptor complex that anchors kinesin to the mitochondrial surface. The phosphorylation of Miro activates proteasomal degradation of Miro in a Parkin-dependent manner.	SIGNOR-272726
P38398	O75367	1	ubiquitination	up-regulates activity	0.2	BRCA1 Ubiquitinates K123 of mH2A1 in a Ligase-Activity-Dependent Manner.	SIGNOR-278752
P31749	P67809	1	phosphorylation	up-regulates	0.558	Phosphorylation of yb-1 at the serine 102 residue is required for transcriptional activation of growth-enhancing genes, such as egfr. Herein, we illustrate that activated akt binds to and phosphorylates the yb-1 cold shock domain at ser102	SIGNOR-252521

P17481

P40426

2

binding

up-regulates activity

0.484

the ability of HoxB8 to heterodimerizes with endogenous Pbx proteins on DNA alters gene transcription in a manner that prevents progression through an intrinsic genetic differentiation program. In conjunction with Pbx, HoxB8 could alter transcription of Pbx target genes by direct or indirect mechanisms.

SIGNOR-223149

Q15011

Q8IUR6

0

transcriptional regulation

up-regulates quantity by expression

0.2

Luman/CREB3 induces transcription of the endoplasmic reticulum (ER) stress response protein Herp through an ER stress response element.

SIGNOR-261575

Q92570

P04637

0

transcriptional regulation

up-regulates quantity by expression

0.264

We showed that p53 directly bound the promoter of NR4A3 gene and induced its transcription. p53 transactivates the NR4A3 promoter in H1299 cells.

SIGNOR-256200

Q92686

P17252

0

phosphorylation

up-regulates activity

0.394

Phosphorylation of RC3 by PKC alpha, beta, or gamma was stimulated by Ca2+, phospholipid, and diacylglycerol. A single site, Ser36, which is adjacent to the predicted calmodulin (CaM)-binding domain, was phosphorylated by these enzymes. Phosphorylation of RC3 by PKC or PKM, a protease-degraded PKC, was inhibited by CaM. The effect of CaM apparently targets at RC3, as phosphorylation of protamine sulfate by PKM was not inhibited by CaM.

SIGNOR-248913

P31751

Q86YS7

1

phosphorylation

up-regulates activity

0.513

MS analysis of an HA-CDP138 sample from the in vitro kinase assay revealed that active Akt2 induces CDP138 phosphorylation at serine (Ser)197, which lies within a consensus Akt substrate motif RQRLIS 197 ( xref ).

SIGNOR-279585

P25490

P07948

0

phosphorylation

down-regulates activity

0.2

In the case of Lyn overexpression, single mutations at either tyrosine 8, 254, or 383 severely reduced Lyn-mediated YY1 phosphorylation, suggesting that these three sites may be targets of Lyn in vivo (Fig. 3, A and B).

SIGNOR-276930

Q9Y2X7

P12931

0

phosphorylation

up-regulates activity

0.542

Tyrosines 246 and 293 are required to hold GIT1 in a closed conformation.Hyperphosphorylation of GIT1-N by Src and pervanadate does not affect its binding in vitro to full length GIT1 proteins. Mutations Y246E and Y293E of GIT1 enhance binding to paxillin.

SIGNOR-276627

P04233

P14174

2

binding

up-regulates

0.735

Mif binds to the extracellular domain of cd74, and cd74 is required for mif-induced activation of the extracellular signal-regulated kinase-1/2 map kinase cascade, cell proliferation, and pge2 production.

SIGNOR-101526

P31994

P07948

0

phosphorylation

up-regulates activity

0.43

Therefore, we conclude that FcgammaRIIb1 phosphorylation upon BCR-FcgammaR coligation is most likely due to BCR-associated Lyn

SIGNOR-249380

Q5JTC6

O15169

1

relocalization

up-regulates activity

0.789

Amer1 binds ck1gamma, recruits axin and gsk3beta to the plasma membrane and promotes complex formation between axin and lrp6.

SIGNOR-171886

Q00535

P50406

1

phosphorylation

down-regulates activity

0.374

Cdk5 phosphorylates the 5-HT6R on serine 350 (Ser350)|This suggests that the 5-HT6R is unable to interact with GPRIN1 when it is phosphorylated by Cdk5.

SIGNOR-264407

Q9GZQ4

P50148

2

binding

up-regulates activity

0.464

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.

SIGNOR-257218

O60716

P48729

0

phosphorylation

up-regulates activity

0.2

Moreover, CK1α phosphorylates p120-catenin on Ser268 and Ser269, releasing this protein from the signalosome and facilitating the subsequent phosphorylation of cadherin and the disruption of this cadherin interaction with LRP5/6

SIGNOR-277893

P20807

P20810

2

binding

down-regulates activity

0.569

In addition to Ca2+, calpastatin has a key role in the regulation of calpain. Calpastatin, a heat-stable protein ranging from ~70 to ~140 kDa of apparent molecular weight depending on the cell type, is considered a specific endogenous inhibitor of calpains|The calpastatin molecule contains four inhibitory units [75–77]. Each of these units binds to one calpain molecule [75–77]. Therefore, the ratio calpain/calpastatin plays a key role in the regulation of calpain activity [78–80]. The inhibitory effect of calpastatin requires Ca2+-dependent high-affinity binding to three sites of calpain

SIGNOR-251603

Q15418

P16220

1

phosphorylation

up-regulates activity

0.747

The rsks phosphorylate the trascription factor creb at serine 133 to promote cell survival.

SIGNOR-72117

P23276

P14138

1

cleavage

up-regulates activity

0.676

These data demonstrate that the Kell blood group protein is a proteolytic enzyme that processes big ET-3, generating ET-3, a potent bioactive peptide with multiple biological roles.

SIGNOR-256354

P45983

Q14934

1

phosphorylation

up-regulates activity

0.467

Here, we showed that the nuclear factor of activated T3 (NFAT3) is phosphorylated by JNK1 or JNK2 at Ser(213) and Ser(217), which are located in the conserved SP motif.|Moreover, a 3xNFAT-luc reporter gene assay indicated that NFAT3 transcriptional activity was increased in a dose dependent manner by JNK1 or JNK2.

SIGNOR-280033

P20823

Q9NPD5

1

transcriptional regulation

up-regulates quantity by expression

0.251

Farnesoid X receptor, hepatocyte nuclear factors 1alpha and 3beta are essential for transcriptional activation of the liver-specific organic anion transporter-2 gene.|This study demonstrated that the transcription of the LST-2 gene is regulated by three transcription factors, FXR, HNF1alpha, and HNF3beta.

SIGNOR-268988

P09874

P49959

1

relocalization

up-regulates activity

0.2

PARP1 collaborates with Mre11 to promote replication fork restart after release from replication blocks, most likely by recruiting Mre11 to the replication fork to promote resection of DNA.

SIGNOR-272478

Q99967

P28482

0

phosphorylation

up-regulates activity

0.454

CITED2 coactivation is enhanced by activation of MAPK1 and requires T166.|CITED2 is phosphorylated by MAPK1 at S85, T166 and T175.

SIGNOR-278410

P46108

P22681

2

binding

up-regulates

0.824

These results indicate that crk binds to c-cbl in a tyrosine phosphorylation-dependent manner.

SIGNOR-39241

P38606

P25490

0

transcriptional regulation

up-regulates quantity by expression

0.325

We investigated the relationship between transcription factor YY1 and ATP6V1A, and found that mRNA expression of YY1 had significant correlation with that of ATP6V1A. To validate that YY1 transcriptionally regulates ATP6V1A, we discovered that the ATP6V1A core promoter region contains three YY1 binding sites. Moreover, RNAi-mediated knockdown of YY1 in GC cells significantly decreased ATP6V1A mRNA and protein expression, while YY1 overexpression increased ATP6V1A expression level.

SIGNOR-260635

P27361

Q15366

1

phosphorylation

up-regulates quantity by stabilization

0.323

We also identified 4 hnRNP-E2 MAPKERK1/2 phosphorylation sites and demonstrated that hnRNP-E2 is a bona fide MAPKERK1/2 substrate and that MAPKERK1/2-dependent phosphorylation of hnRNP-E2 at these amino acid residues is essential for increased hnRNP-E2 expression in BCR/ABL-expressing cells. Serine/threonine to alanine substitution abolishes hnRNP-E2 phosphorylation and markedly decreases its stability in BCR/ABL-expressing myeloid precursors. Consistent with the existence of a BCR/ABL-MAPK pathway that posttranslationally regulates hnRNP-E2 expression, sequence analysis of hnRNP-E2 revealed the presence of 4 consensus ERK phosphorylation sites (S/T-P)35,36 at amino acid residues 173, 189, 213, and 272 (Figure 2B).

SIGNOR-262916

Q96BA8

2

binding

up-regulates activity

0.2

E4BP4, ATF-6, OASIS, and XBP-1 all formed strong homodimeric associations on the array Transcription factor dimerization can increase the selectivity of protein-DNA interactions and generate a large amount of DNA binding diversity from a relatively small number of proteins

SIGNOR-224205

P26012

O14713

2

binding

down-regulates activity

0.313

Integrins also bind to many PTBdomain-containing proteins (Calderwood et al., 2003) – including Dok1 and integrincytoplasmic-domain-associated protein 1 (ICAP1) – and these can compete with talin for binding to integrin and so can impair activation

SIGNOR-257667

P53701

P99999

1

chemical modification

up-regulates activity

0.44

Cytochrome c oxidase catalyzes the reduction of molecular oxygen to water, a process in which four electrons, four protons, and one molecule of oxygen are consumed. The reaction is coupled to the pumping of four additional protons across the membrane. According to the currently accepted concept, the pumping of all four protons occurs after the binding of oxygen to the reduced enzyme and is exclusively coupled to the last two electron transfer steps.

SIGNOR-280296

Q92918

P00519

0

phosphorylation

up-regulates activity

0.379

C-Abl phosphorylates HPK1 in cytoplasm and stimulates HPK1 activity. the c-Abl phosphorylation site (YXXP) in HPK1 (Y232QPP; aa 232–235) is localized in HPK1-KD

SIGNOR-251429

Q14457

P46934

0

ubiquitination

up-regulates quantity by stabilization

0.46

BECN1 stability was increased by NEDD4 via K6 and K27 ubiquitination during autophagy induction, thereby promoting autophagy activation.|Further, NEDD4 mediated K6- and K27- linkage ubiquitination of BECN1, leading to elevated stability of BECN1 and increased autophagy.

SIGNOR-278558

P00519

P46527

1

phosphorylation

down-regulates quantity

0.595

A conserved tyrosine residue (Y88) in the Cdk-binding domain of p27 can be phosphorylated by the Src-family kinase Lyn and the oncogene product BCR-ABL

SIGNOR-245293

Q13153

P53667

1

phosphorylation

up-regulates activity

0.614

Activation of lim-kinase by pak1 couplesp21-activated kinase (pak1) phosphorylates lim-kinase at threonine residue 508 within lim-kinase's activation loop

SIGNOR-72142

O94761

Q7L590

2

binding

down-regulates

0.509

Mcm10 inhibits recq4 helicase activity.

SIGNOR-187701

Q96TA1

P01112

2

binding

up-regulates activity

0.2

EGFR phosphorylates FAM129B, resulting in binding of phosphorylated FAM129B to H-Ras and reduced the association of p120-RasGAP with H-Ras, thereby enhancing H-Ras activation for ERK1/2-dependent β-catenin transactivation for enhanced Warburg effect, tumor cell proliferation, and brain tumorigenesis.

SIGNOR-273659

P62837

Q9UPQ7

2

binding

up-regulates activity

0.385

Our initial tests of various E2s showed that the RING domain of PDZRN3 exhibits ubiquitin ligase activity in the presence of E1 and the UbcH5 family of E2 enzymes (Fig. 3 A). Consistent with this finding, GST pull-down assays showed that PDZRN3 directly interacts with the UbcH5B ubiquitin conjugating enzyme (Fig. 3 B).

SIGNOR-271663

P12931

P10301

1

phosphorylation

down-regulates activity

0.58

The small gtpase, r-ras, affects cell adhesion by maintaining integrin activity. Activated src oncogene phosphorylates r-ras and suppresses integrin activity. the src phosphorylation site in r-ras was tyrosine 66

SIGNOR-111189

Q9UNE7

Q15797

1

ubiquitination

down-regulates

0.328

These results suggest that chip can interact with the smad1/smad4 proteins and block bmp signal transduction through the ubiquitin-mediated degradation of smad proteins.

SIGNOR-120731

Q86U86

Q13049

0

ubiquitination

down-regulates quantity by destabilization

0.2

TRIM32 ubiquitination of PB1 leads to its protein degradation.

SIGNOR-278735

Q969Q1

P61088

0

ubiquitination

up-regulates activity

0.539

We used MuRF1 as the E3 as it functions with all these E2s to ubiquitinate one of its typical substrates, troponin I Although UbcH1 and UbcH13/Uev1a support ubiquitination of troponin I by MuRF1, these E2s do not support ubiquitination of S5a, unlike Class I E2s.

SIGNOR-272737

P31751

P03372

1

phosphorylation

up-regulates activity

0.509

AKT activate ERalpha in the absence of estrogen. The consensus AKT phosphorylation site Ser-167 of ERalpha is required for phosphorylation and activation by AKT.

SIGNOR-251490

P30047

P30793

2

binding

down-regulates activity

0.864

The enzyme activity of GTP cyclohydrolase I is controlled by a regulatory protein for this enzyme, GFRP, which is a pentamer of identical subunits. GFRP mediates feedback inhibition of GTP cyclohydrolase I activity by BH4, and the inhibition by BH4 is reversed by phenylalanine

SIGNOR-252203

Q15643

P10827

2

binding

up-regulates

0.387

Trip230 binds to rb independently of thyroid hormone while it forms a complex with tr in a thyroid hormone-dependent manner. Ectopic expression of the protein trip230 in cells, but not a mutant form that does not bind to tr, enhances specifically tr-dependent transcriptional activity.

SIGNOR-50348

Q13885

Q14980

2

binding

up-regulates

0.2

Direct binding of numa to tubulin is mediated by a novel sequence motif in the tail domain that bundles and stabilizes microtubules.

SIGNOR-116936

Q8NER1

P29350

0

dephosphorylation

down-regulates activity

0.2

Shp-1 dephosphorylates TRPV1 in dorsal root ganglion neurons and alleviates CFA-induced inflammatory pain in rats.|These results suggested that Shp-1 dephosphorylated and inhibited TRPV1 in DRG neurons, contributing to maintain thermal nociceptive thresholds in normal rats, and as a compensatory mechanism, Shp-1 increased in DRGs of rats with CFA-induced inflammatory pain, which was involved in protecting against excessive thermal hyperalgesia.

SIGNOR-277129

P48431

P31749

0

phosphorylation

up-regulates quantity by stabilization

0.532

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

SIGNOR-279003

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

O14795

Q86UR5

0

relocalization

up-regulates activity

0.798

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-264385

Q15796

Q96PU5

0

ubiquitination

down-regulates activity

0.781

Through its ww domain, nedd4l specifically recognizes a tgf-beta-induced phosphothr-protyr motif in the linker region, resulting in smad2/3 polyubiquitination and degradation

SIGNOR-217622

Q15637

P18146

2

binding

up-regulates activity

0.295

GNRH1 induces expression of early growth response 1 (EGR1), which interacts with steroidogenic factor 1 (SF1) and paired-like homeodomain transcription factor 1 (PITX1) to regulate Lhb promoter activity.

SIGNOR-254914

Q96KG9

P31749

0

phosphorylation

up-regulates activity

0.255

In previous work, we demonstrated that TEIF (transcriptional element-interacting factor) distributes in the centrosomes and regulates centrosome status under both physiologic and pathologic conditions.|A consensus motif for Akt phosphorylation (RHRVLT) proved to be involved in centrosomal TEIF localization, and the 469-threonine of this motif may be phosphorylated by Akt both in vitro and in vivo. Elimination of this phosphorylated site on TEIF caused reduced centrosome distribution and centrosome splitting or amplification.

SIGNOR-265496

Q86UT6

Q9Y4K3

2

binding

down-regulates activity

0.472

Immunoprecipitation experiments showed that NLRX1 interacted with TRAF6 and TRAF3, but not with TRAF2 or TRAF5. These results further suggest that NLRX1 specifically inhibits TLR-induced TRAF6-dependent NF-kB signaling through targeting TRAF6.

SIGNOR-260364

Q99759

Q13501

1

phosphorylation

up-regulates activity

0.556

MEKK3 overexpression, but not that of a kinase dead mutant, was able to induce the phosphorylation of p62 at T269 and S272 (XREF_FIG), which correlated with mTORC1 activation (XREF_FIG), suggesting that MEKK3 could be a bona fide regulator of p62 phosphorylation and mTORC1 activity.

SIGNOR-279532

O14733

Q9UQF2

2

binding

up-regulates

0.722

Both jip1 and jip2 selectively bind the mapkk isoform mkk7.

SIGNOR-70848

P07951

P48736

0

phosphorylation

up-regulates activity

0.335

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

SIGNOR-263028

P00533

O14939

1

phosphorylation

up-regulates activity

0.516

Using transiently transfected human embryonic kidney fibroblasts (HEK293), we demonstrate here that PLD1 activity, and to a lesser extent PLD2 activity, is stimulated in response to epidermal growth factor (EGF). PLD2, but not PLD1, associates with the EGF receptor in a ligand-independent manner and becomes tyrosine-phosphorylated upon EGF receptor activation. Tyrosine 11 (Tyr-11) of PLD2 was identified as the specific phosphorylation site. Mutation of this residue to phenylalanine enhanced basal activity almost 2-fold

SIGNOR-251095

O43597

Q9BUB5

0

phosphorylation

down-regulates

0.531

The spry2/nedd4 association involves the ww domains of nedd4 and requires phosphorylation of the mnk2 kinase sites, ser(112) and ser(121), on spry2. mnk2 silencing decreased spry2-nedd4 interactions and also augmented the ability of spry2 to inhibit fibroblast growth factor signaling. endogenous and overexpressed nedd4 polyubiquitinate spry2 via lys(48) on ubiquitin and decrease its stability.

SIGNOR-188889

O43683

Q12834

1

phosphorylation

down-regulates activity

0.992

Bub1 directly phosphorylates Cdc20 in vitro and inhibits the ubiquitin ligase activity of APC/C(Cdc20) catalytically. A Cdc20 mutant with all six Bub1 phosphorylation sites removed is refractory to Bub1-mediated phosphorylation and inhibition in vitro.

SIGNOR-250606

P18887

P68400

0

phosphorylation

up-regulates

0.395

Xrcc1 phosphorylation by ck2 is required for its stability and efficient dna repair

SIGNOR-165419

Q00535

Q8NEB9

1

phosphorylation

down-regulates

0.357

Thr159 phosphorylation negatively regulates the ptdins3 kinase activity of vps34 and autophagy cdk5/p25, a neuronal cdk shown to play a role in alzheimer's disease, can also phosphorylate thr159 of vps34.

SIGNOR-165772

Q16549

P30305

1

phosphorylation

down-regulates

0.2

We propose that regulation of cdc25b phosphorylation by p38 is a critical event for initiating the g2/m checkpoint after ultraviolet radiation

SIGNOR-107423

Q96L34

Q15831

0

phosphorylation

up-regulates

0.535

Lkb1 is a master kinase that activates 13 kinases of the ampk subfamily, including mark/par-1we recently demonstrated that the lkb1 tumour suppressor kinase, in complex with the pseudokinase strad and the scaffolding protein mo25, phosphorylates and activates amp-activated protein kinase (ampk). A total of 12 human kinases (nuak1, nuak2, brsk1, brsk2, qik, qsk, sik, mark1, mark2, mark3, mark4 and melk) are related to ampk. Here we demonstrate that lkb1 can phosphorylate the t-loop of all the members of this subfamily, apart from melk, increasing their activity >50-fold

SIGNOR-122682

O96017

Q15717

1

phosphorylation

down-regulates activity

0.55

Given the fact that Chk2 phosphorylates HuR at residues S88, S100 and T118 and that each individual phosphorylation site by Chk2 plays a distinct role in regulating HuR- binding to different target mRNAs (22,42), we further tested HuR mutants with alanine substitutions at each of the Chk2 phosphorylation sites.

SIGNOR-278163

P26447

P35579

2

binding

down-regulates activity

0.418

Our results show that S100A4 regulates cell polarization during directed motility by affecting the localization of protrusions through interactions with myosin-IIA, with S100A4 expressing cells displaying few side protrusions and extensive forward protrusions during chemotaxis compared with control cells. The mechanisms by which these antibodies and S100A4 increase protrusive activity and promote cellular motility are not well understood, but the observation that S100A4 can inhibit the actin-activated ATPase of myosin-IIA (34) suggests that S100A4 could function as a myosin-IIA inhibitor in vivo.

SIGNOR-269282

Q9UKV5

P04114

1

ubiquitination

down-regulates quantity by destabilization

0.29

In physiological condition, the unnecessary apoB is usually ubiquitinated by E3 ligase AMFR, and subsequently degraded by ubiquitination proteasomes.

SIGNOR-278685

Q00987

Q9UN86

2

binding

down-regulates activity

0.3

G3BP2 binds to MDM2 and decreases its E3 ligase activity. The G3BP2 isoform additionally associated with murine double minute 2 (MDM2), a negative regulator of p53. G3BP2 expression resulted in significant reduction in MDM2-mediated p53 ubiquitylation and degradation.

SIGNOR-278892

P49137

P50549

1

phosphorylation

up-regulates

0.612

Neverthless, some transcription factors, such as e47, er81, srf and creb are also phosphorylated by mk2

SIGNOR-166625

P49674

O15534

1

phosphorylation

down-regulates quantity by destabilization

0.842

We show here that mPer proteins, negative limbs of the autoregulatory loop, are specific substrates for CKIepsilon and CKIdelta. The CKI phosphorylation of mPer1 and mPer3 proteins results in their rapid degradation, which is dependent on the ubiquitin-proteasome pathway.

SIGNOR-267997

P49459

P24941

0

phosphorylation

up-regulates

0.374

Hhr6a is phosphorylated in vitro by cdk-1 and -2 on ser120, a residue conserved in all hhr6a homologues, resulting in a 4-fold increase in its ubiquitin-conjugating activity.

SIGNOR-116508

O94782

Q9BXW9

1

deubiquitination

down-regulates activity

0.761

The deubiquitinating enzyme USP1 controls the cellular levels of the DNA damage response protein Ub-FANCD2|The level of monoubiquitinated FANCD2 protein increases in response to various types of DNA damage in mammalian cells

SIGNOR-263273

Q13144

P05198

1

guanine nucleotide exchange factor

up-regulates activity

0.84

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-269123

P17612

P13612

1

phosphorylation

up-regulates activity

0.494

PKA phosphorylationin vitro blocks the binding of the alpha4 tail to paxillin. A mutation that mimics alpha4 phosphorylation disrupts paxillin binding and promotes cell spreading

SIGNOR-110119

P08754

P31391

2

binding

up-regulates activity

0.45

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.

SIGNOR-256823

P61586

O94989

0

guanine nucleotide exchange factor

up-regulates activity

0.571

We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).

SIGNOR-260540

Q96EP1

P09874

1

polyubiquitination

down-regulates quantity by destabilization

0.427

Here, we show that checkpoint with Forkhead-associated (FHA) and RING finger domain protein (CHFR), an E3 ubiquitin ligase, is recruited to DSBs by poly(ADP-ribose) (PAR). Moreover, CHFR ubiquitinates PAR polymerase 1 (PARP1) and regulates chromatin-associated PARP1 in vivo. Moreover, the poly-ubiquitin chain on PARP1 could be recognized by both anti-K48 and K63-linked poly-ubiquitin chain antibodies, suggesting that CHFR mediates a mixed poly-ubiquitin chain linkage on PARP1. With MG132 treatment, ubiquitinated PARP1 was significantly accumulated (Figure 4D), suggesting that the ubiquitination of PARP1 is likely involved in protein degradation. Consistently, we found that following DNA damage, PARP1 quickly dissociated from the chromatin in the wild-type cells (Figure 4F). However, in the Chfr−/− cells, the dissociation of PARP1 from the chromatin was significantly delayed.

SIGNOR-271470

P22681

P29376

0

phosphorylation

up-regulates

0.369

Although c-cbl is found to be phosphorylated by ltk and therefore is a second candidate linking ltk with the pi3-kinase pathway along with irs-1, we found that the p85 subunit of pi3 kinase directly binds to tyrosine 753 of ltk, which is located within a yxxm motif, a consensus binding amino acid sequence for the sh2 domain of p85.

SIGNOR-49528

P01106

P30279

1

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

O15182

Q15154

0

relocalization

up-regulates

0.297

Rna silencing of pcm-1 leads to reduced assembly of centrin, pericentrin, and ninein at the centrosome

SIGNOR-95016

Q99835

P59768

2

binding

up-regulates

0.385

Consistent with its predicted topology, smo couples to a specific family of inhibitory g protein (gis) to regulate hh signaling.

SIGNOR-199183

P78356

Q16539

0

phosphorylation

down-regulates

0.2

Inhibition of pip4kbeta activity occurs through the direct phosphorylation of pip4kbeta at ser326 by the p38 stress-activated protein kinase.

SIGNOR-149359

P24941

P98177

1

phosphorylation

down-regulates

0.518

Additionally, ck1, dyrk1a, and cdk2 also phosphorylate foxos at various sites to inhibit foxos activity

SIGNOR-183655

Q92547

Q13535

2

binding

up-regulates activity

0.814

These results establish that TopBP1 can activate both Xenopus and human ATR. Furthermore, these experiments provide conclusive evidence that the kinase activity that is induced by TopBP1 is intrinsic to the ATR protein itself and is not due to a kinase that associates with ATR.

SIGNOR-263232

P42345

O75385

1

phosphorylation

down-regulates activity

0.849

mTORC1, which is often referred to as the gatekeeper to autophagy, is a key regulator of the Ulk1-Atg13-FIP200 kinase complex.11,14,25 Under nutrient-rich conditions, active mTORC1 associates with and inactivates the Ulk1-Atg13-FIP200 complex by phosphorylating Ulk1 and Atg13.

SIGNOR-183903

P11308

P04628

1

transcriptional regulation

up-regulates quantity by expression

0.2

Interestingly, our data showed that ERG drastically induced Wnt ligand gene expression.

SIGNOR-261597

P31994

Q86YJ5

0

ubiquitination

down-regulates quantity by destabilization

0.2

MARCH9, a member of the RING-CH family of transmembrane E3 ubiquitin ligases, down-regulates CD4, major histocompatibility complex-I (MHC), and ICAM-1 in lymphoid cells. To identify novel MARCH9 substrates, we used high throughput flow cytometry and quantitative mass spectrometry by stable isotope labeling by amino acids in cell culture (SILAC) to determine the differential expression of plasma membrane proteins in a MARCH9-expressing B cell line. This combined approach identified 13 potential new MARCH9 targets.

SIGNOR-271541

P62834

O95398

0

guanine nucleotide exchange factor

up-regulates activity

0.71

Epac1 (cAMP-GEFI) and Epac2 (cAMP-GEFII) are closely related guanine nucleotide exchange factors (GEFs) for the small GTPase Rap1, which are directly regulated by cAMP. Here we show that both GEFs efficiently activate Rap2 as well.

SIGNOR-263956

Q8IW41

P47712

1

phosphorylation

up-regulates activity

0.334

The p38-activated protein kinases MNK1, MSK1, and PRAK1 phosphorylate cPLA2 in vitro uniquely on Ser-727. By using Chinese hamster ovary, HeLa, and HEK293 cells stably transfected with wild type and phosphorylation site mutant forms of cPLA2, we show that phosphorylation of cPLA2 at both Ser-505 and Ser-727 and elevation of Ca(2+) leads to its activation in agonist-stimulated cells.

SIGNOR-250162

P38398

Q9H4M3

2

binding

down-regulates quantity by destabilization

0.369

The F-box protein FBXO44 mediates BRCA1 ubiquitination and degradation. The Skp1-Cul1-F-box-protein44 (SCF(FBXO44)) complex ubiquitinates full-length BRCA1 in vitro.

SIGNOR-272037

Q14344

Q9HC97

2

binding

up-regulates activity

0.2

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.

SIGNOR-257283

P78527

Q14653

1

phosphorylation

up-regulates

0.43

Phosphorylation of irf-3 by dna-pk after virus infection results in its nuclear retention and delayed proteolysis

SIGNOR-115331

O15033

Q9NR28

1

ubiquitination

down-regulates quantity by destabilization

0.377

AREL1 ubiquitinated SMAC, primarily on Lys62 and Lys191 |E701A substitution in the AREL1 HECT domain substantially increased its autopolyubiquitination and SMAC ubiquitination activity, whereas deletion of the last three amino acids at the C terminus completely abrogated AREL1 autoubiquitination and reduced SMAC ubiquitination.

SIGNOR-267672

Q96RI1

Q05513

0

phosphorylation

up-regulates

0.38

The effect of fic1 on fxr phosphorylation and nuclear localization and its effects on bsep promoter activity could be blocked with protein kinase c zeta (pkc zeta) inhibitors (pseudosubstrate or small interfering rna silencing). Recombinant pkc zeta directly phosphorylated immunoprecipitated fxr. The mutation of threonine 442 of fxr to alanine yielded a dominant negative protein,

SIGNOR-179771

P28482

Q86U44

1

phosphorylation

up-regulates quantity by stabilization

0.273

Mass spectrometry analysis showed that ERK phosphorylates METTL3 at three highly conserved residues: S43, S50, and S525 (Figures 2D and 2E). Mutational analysis further confirmed these three sites as main ERK phosphorylation sites (Figure 2F). Phosphorylation of METTL3 increases interaction with USP5, decreasing ubiquitination to stabilize the m6 A methyltransferase complex.

SIGNOR-265948

P06241

Q9NWQ8

1

phosphorylation

up-regulates activity

0.703

Thus, Fyn mediates Csk-binding protein-Csk interaction and recruits Csk to rafts by phosphorylating Csk-binding protein.

SIGNOR-279987

Q96PZ7

P84022

2

binding

up-regulates activity

0.2

CSMD1 co-immunoprecipitated with SMAD3, confirming our results that CSMD1 interacts with Smad3 in A375 cells. CSMD1 interacts with Smad3 and induces phosphorylation (p-Smad3). Phosphorylated Smad3 promotes Smad2 phosphorylation and Smad2/3/4 complex formation.

SIGNOR-265151

P42224

P40763

0

transcriptional regulation

up-regulates quantity by expression

0.615

In summary, we report in this study that STAT1 expression is upregulated by nuclear EGFR, EGFRvIII and HER2, and that STAT3 synergizes with the three receptors to further enhance STAT1 expression. These novel findings establish a novel link between the mitogenic ErbB signaling pathway and the inflammatory pathway mediated by STAT1. The oncogenic transcription factor STAT3 binds to the STAT1 promoter and synergizes with nuclear EGFR to significantly enhance STAT1 gene expression.

SIGNOR-263650

Q6UXZ4

P43146

2

binding

down-regulates activity

0.584

In the presence of netrin-1, UNC5 co-immuno-precipitates with DCC, suggesting the formation of a ternary complex of netrin-1 with ecto-domains of DCC and UNC5. DCC binding to netrin-1 alone leads to axon attraction. Importantly, DCC has the ability to switch the netrin-1-mediated responses from attraction to repulsion when another receptor UNC5 co-exists. DCC binding to netrin-1 alone leads to axon attraction. Importantly, DCC has the ability to switch the netrin-1-mediated responses from attraction to repulsion when another receptor UNC5 co-exists.

SIGNOR-268167

Q12955

Q92823

0

relocalization

up-regulates quantity

0.721

Neurofascin, L1, NrCAM, NgCAM, and neuroglian are membrane-spanning cell adhesion molecules with conserved cytoplasmic domains that are believed to play important roles in development of the nervous system. This report presents biochemical evidence that the cytoplasmic domains of these molecules associate directly with ankyrins, a family of spectrin-binding proteins located on the cytoplasmic surface of specialized plasma membrane domains.

SIGNOR-266720

Q12923

P12931

1

dephosphorylation

down-regulates activity

0.54

Mechanistically, RIL suppresses Src activation through interacting with Src and PTPL1, allowing PTPL1 dependent dephosphorylation of Src at the activation loop.|Our results reveal a novel Src inactivation cycle in which reversion-induced LIM preferentially recognizes active Src and facilitates PTPL1-mediated inactivation of Src.

SIGNOR-277125

Q13144

P49840

0

phosphorylation

down-regulates activity

0.368

We identify multiple phosphorylation sites in the largest, catalytic, subunit (epsilon) of mammalian eIF2B. Glycogen synthase kinase 3 (GSK3) is responsible for phosphorylating Ser535. This regulatory phosphorylation event requires both the fourth site (Ser539) and a distal region, which acts to recruit GSK3 to eIF2Bepsilon in vivo. eIF2Bϵ from mammals or insects is a substrate for glycogen synthase kinase 3 (GSK3), and this inhibits the activity of eIF2B

SIGNOR-251215

O60260

Q8IXI1

1

polyubiquitination

down-regulates quantity by destabilization

0.2

PINK1 phosphorylates Miro, a component of the primary motor/adaptor complex that anchors kinesin to the mitochondrial surface. The phosphorylation of Miro activates proteasomal degradation of Miro in a Parkin-dependent manner.

SIGNOR-272726

P38398

O75367

1

ubiquitination

up-regulates activity

0.2

BRCA1 Ubiquitinates K123 of mH2A1 in a Ligase-Activity-Dependent Manner.

SIGNOR-278752

P31749

P67809

1

phosphorylation

up-regulates

0.558

Phosphorylation of yb-1 at the serine 102 residue is required for transcriptional activation of growth-enhancing genes, such as egfr. Herein, we illustrate that activated akt binds to and phosphorylates the yb-1 cold shock domain at ser102

SIGNOR-252521