| + |
MAP3K5 | up-regulates quantity by stabilization 
phosphorylation
|
DAXX |
0.75 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-109680 |
Ser176 |
TNAENTAsQSPRTRG |
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 19789335 |
we show that TNFalpha treatment induces the accumulation of Daxx protein through ASK1 activation by preventing its proteasome-dependent degradation. ASK1 directly phosphorylates Daxx at Ser(176) and Ser(184) and Daxx is required for the sustained activation of JNK. Our results indicate that Daxx not only activates ASK1 but also is a downstream target of ASK1 and that accumulated Daxx further activates ASK1. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-109684 |
Ser184 |
QSPRTRGsRRQIQRL |
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 19789335 |
we show that TNFalpha treatment induces the accumulation of Daxx protein through ASK1 activation by preventing its proteasome-dependent degradation. ASK1 directly phosphorylates Daxx at Ser(176) and Ser(184) and Daxx is required for the sustained activation of JNK. Our results indicate that Daxx not only activates ASK1 but also is a downstream target of ASK1 and that accumulated Daxx further activates ASK1. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
MAP3K5 | up-regulates
phosphorylation
|
DAXX |
0.75 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-188321 |
Ser176 |
TNAENTAsQSPRTRG |
Homo sapiens |
|
| pmid |
sentence |
| 19789335 |
Our data demonstrated that ask1 controls the cytoplasmic localization of daxx (fig.1). our results indicate that daxx not only activates ask1 but also is a downstream target of ask1 and that accumulated daxx further activates ask1. Thus, the daxx-ask1 positive feedback loop amplifying jnk/p38 signaling plays an important role in the cell-killing effects of stressors, such as tnfalpha. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-188325 |
Ser184 |
QSPRTRGsRRQIQRL |
Homo sapiens |
|
| pmid |
sentence |
| 19789335 |
Our data demonstrated that ask1 controls the cytoplasmic localization of daxx (fig.1). our results indicate that daxx not only activates ask1 but also is a downstream target of ask1 and that accumulated daxx further activates ask1. Thus, the daxx-ask1 positive feedback loop amplifying jnk/p38 signaling plays an important role in the cell-killing effects of stressors, such as tnfalpha. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
MAP3K5 | up-regulates activity
phosphorylation
|
MAP2K3 |
0.45 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-161763 |
Ser218 |
ISGYLVDsVAKTMDA |
Homo sapiens |
|
| pmid |
sentence |
| 19920149 |
Ask1 is a member of a mapkkk family and functions as an upstream kinase engaged in c-jun nh2-terminal kinase (jnk)/p38 signaling via the phosphorylation and activation of mapkks, such as mkk3, -4, -6, and -7 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-226672 |
|
|
Chlorocebus aethiops |
COS Cell |
| pmid |
sentence |
| 8974401 |
ASK1 activated SEK1 and MKK3 up to 7.0- and 11.8-fold, respectively |
|
| Publications: |
2 |
Organism: |
Homo Sapiens, Chlorocebus Aethiops |
| Pathways: | P38 Signaling, P38 Signaling and Myogenesis, TNF alpha |
| + |
MAP3K5 | up-regulates
phosphorylation
|
ZNF622 |
0.42 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-175113 |
Ser314 |
WCNEKGKsFYSTEAV |
Homo sapiens |
|
| pmid |
sentence |
| 21771788 |
Ask1 directly phosphorylated zpr9 at ser(314) and thr(318), suggesting that zpr9 can act as an ask1 substrate. Ask1-mediated phosphorylation of zpr9 at ser(314) and thr(318) was also responsible for zpr9-induced apoptosis. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-175117 |
Thr318 |
KGKSFYStEAVQAHM |
Homo sapiens |
|
| pmid |
sentence |
| 21771788 |
Ask1 directly phosphorylated zpr9 at ser(314) and thr(318), suggesting that zpr9 can act as an ask1 substrate. Ask1-mediated phosphorylation of zpr9 at ser(314) and thr(318) was also responsible for zpr9-induced apoptosis. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
AKT | down-regulates activity 
phosphorylation
|
MAP3K5 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-104646 |
Ser83 |
ATRGRGSsVGGGSRR |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 11154276 |
Akt phosphorylates and negatively regulates apoptosis signal-regulating kinase 1 akt decreased ask1 kinase activity stimulated by both oxidative stress and overexpression in 293 cells by phosphorylating a consensus akt site at serine 83 of ask1. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
AKT2 | down-regulates activity
phosphorylation
|
MAP3K5 |
0.36 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-100588 |
Ser83 |
ATRGRGSsVGGGSRR |
Homo sapiens |
Breast Cancer Cell |
| pmid |
sentence |
| 12697749 |
Akt2 interacts with and phosphorylates ask1 at ser-83 resulting in inhibition of its kinase activity |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | P38 Signaling and Myogenesis |
| + |
PIM1 | down-regulates
phosphorylation
|
MAP3K5 |
0.28 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-187905 |
Ser83 |
ATRGRGSsVGGGSRR |
Homo sapiens |
NCI-H1299 Cell |
| pmid |
sentence |
| 19749799 |
Pim1 phosphorylates and negatively regulates ask1-mediated apoptosispim1 phosphorylation of ask1 on ser83 inhibited ask1-mediated c-jun n-terminal kinase phosphorylation |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
AKT1 | down-regulates activity
phosphorylation
|
MAP3K5 |
0.15 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-252465 |
Ser83 |
ATRGRGSsVGGGSRR |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 11154276 |
Akt phosphorylates and negatively regulates apoptosis signal-regulating kinase 1 akt decreased ask1 kinase activity stimulated by both oxidative stress and overexpression in 293 cells by phosphorylating a consensus akt site at serine 83 of ask1. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | P38 Signaling and Myogenesis |
| + |
PP2Ca_R1A_Bd | up-regulates activity
dephosphorylation
|
MAP3K5 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-254756 |
Ser966 |
NEYLRSIsLPVPVLV |
Homo sapiens |
|
| pmid |
sentence |
| 27858941 |
DAB2IP also mediates recruitment of PP2A to ASK1, binding both proteins through its C2 domain; this favors removal of the inhibitory S967 phosphorylation and further activation of ASK1 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MAP3K5 | up-regulates
phosphorylation
|
CDKN1A |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-153440 |
Ser98 |
GGRRPGTsPALLQGT |
Homo sapiens |
|
| pmid |
sentence |
| 17325029 |
P21cip1 is phosphorylated in vitro by both ask1 and jnk1 at s98. /phosphorylation of p21cip1 at s98, which in vivo appears to be regulated by ask1, may therefore mediate negative feedback in the ask1 signaling pathway. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MAP3K5 | up-regulates activity
phosphorylation
|
MAP2K4 |
0.82 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-45373 |
Thr261 |
LVDSIAKtRDAGCRP |
Homo sapiens |
|
| pmid |
sentence |
| 8974401 |
A map kinase kinase kinase (mapkkk), termed ask1, was identified that activated two different subs of map kinase kinases (mapkk), sek1 (or mkk4) and mkk3/mapkk6 (or mkk6), which in turn activated stress-activated protein kinase (sapk, also known as jnk;c-jun amino-terminal kinase) |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-45366 |
|
|
Homo sapiens |
COS-7 Cell |
| pmid |
sentence |
| 8974401 |
A MAP kinase kinase kinase (MAPKKK), termed ASK1, was identified that activated two different subgroups of MAP kinase kinases (MAPKK), SEK1 (or MKK4) and MKK3/MAPKK6 (or MKK6), which in turn activated stress-activated protein kinase (SAPK, also known as JNK; c-Jun amino-terminal kinase) and p38 subgroups of MAP kinases, respectively. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | P38 Signaling, P38 Signaling and Myogenesis, TNF alpha |
| + |
MAP3K5 | up-regulates activity
phosphorylation
|
MAP3K5 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-158423 |
Thr813 |
GDNVLINtYSGVLKI |
Homo sapiens |
|
| pmid |
sentence |
| 17937911 |
Reporter gene assays showed that all three identified in vitro autophosphorylation sites (thr813, thr838, thr842) regulate ask1 signalingmutation of thr838 drastically reduced reporter gene activity when compared to unstimulated control levels. Interestingly, mutation of the other two sites also provided a significant reduction in ask1 function (figure 6a), suggesting that autophosphorylation at the residues thr842 and thr813 regulates ask1 signaling. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-158427 |
Thr838 |
GINPCTEtFTGTLQY |
Homo sapiens |
|
| pmid |
sentence |
| 17937911 |
Reporter gene assays showed that all three identified in vitro autophosphorylation sites (thr813, thr838, thr842) regulate ask1 signalingmutation of thr838 drastically reduced reporter gene activity when compared to unstimulated control levels. Interestingly, mutation of the other two sites also provided a significant reduction in ask1 function (figure 6a), suggesting that autophosphorylation at the residues thr842 and thr813 regulates ask1 signaling. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-158431 |
Thr842 |
CTETFTGtLQYMAPE |
Homo sapiens |
|
| pmid |
sentence |
| 17937911 |
Reporter gene assays showed that all three identified in vitro autophosphorylation sites (thr813, thr838, thr842) regulate ask1 signalingmutation of thr838 drastically reduced reporter gene activity when compared to unstimulated control levels. Interestingly, mutation of the other two sites also provided a significant reduction in ask1 function (figure 6a), suggesting that autophosphorylation at the residues thr842 and thr813 regulates ask1 signaling. |
|
| Publications: |
3 |
Organism: |
Homo Sapiens |
| Pathways: | P38 Signaling, P38 Signaling and Myogenesis, TNF alpha |
| + |
PPM1L | down-regulates
dephosphorylation
|
MAP3K5 |
0.36 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-154554 |
Thr838 |
GINPCTEtFTGTLQY |
Homo sapiens |
|
| pmid |
sentence |
| 17456047 |
Exogenous pp2cepsilon associated with exogenous ask1 in hek-293 cells under non-stressed conditions, inactivating ask1 by decreasing thr845 phosphorylation |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Brain, Kidney |
| + |
PPP5C | down-regulates activity
dephosphorylation
|
MAP3K5 |
0.53 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-111301 |
Thr838 |
GINPCTEtFTGTLQY |
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 11689443 |
Pp5 directly dephosphorylated an essential phospho-threonine residue within the kinase domain of ask1 and thereby inactivated ask1 activity in vitro and in vivo. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-248540 |
Thr842 |
CTETFTGtLQYMAPE |
Mus musculus |
|
| pmid |
sentence |
| 11689443 |
After exposure of cells to H2O2, ASK1 is transiently activated by autophosphorylation at Thr845. The protein then associates with PP5 (protein serine/threonine phosphatase 5), which inactivates ASK1 by dephosphorylation of Thr845. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens, Mus Musculus |
| + |
JAK2 | down-regulates
phosphorylation
|
MAP3K5 |
0.12 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-184600 |
Tyr718 |
IPERDSRySQPLHEE |
Homo sapiens |
|
| pmid |
sentence |
| 19287004 |
Previously we have shown that tyrosine 718 of ask1 when phosphorylated is critical for socs1 binding and socs1-mediated degradation of ask1we identified jak2 and shp2 as a tyr-718-specific kinase and phosphatase, respectively. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PTPN11 | up-regulates
dephosphorylation
|
MAP3K5 |
0.08 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-184604 |
Tyr718 |
IPERDSRySQPLHEE |
Homo sapiens |
|
| pmid |
sentence |
| 19287004 |
Previously we have shown that tyrosine 718 of ask1 when phosphorylated is critical for socs1 binding and socs1-mediated degradation of ask1we identified jak2 and shp2 as a tyr-718-specific kinase and phosphatase, respectively. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SLK | up-regulates
phosphorylation
|
MAP3K5 |
0.45 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-142665 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16316999 |
Induction of apoptosis by the ste20-like kinase slk, a germinal center kinase that activates apoptosis signal-regulating kinase and p38 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Kidney |
| + |
MAPK1 | up-regulates 
unknown
|
MAP3K5 |
0.11 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-146751 |
|
|
Homo sapiens |
Neutrophil |
| pmid |
sentence |
| 16709866 |
The role of members of the arrestin family to mediate kinase activation is also a well-established phenomenon, including activation of members of the src family, erk1/2, and jnk3. Activation often includes the recruitment and interaction of arrestins with upstream mapks (ask1, mek3, mkk3, and mek kinase-2). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
14-3-3 | down-regulates
binding
|
MAP3K5 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-69408 |
|
|
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 10411906 |
14-3-3 may suppress ask1-induced cell death by directly inhibiting the catalytic activity of ask1. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
HSPA2 | down-regulates
binding
|
MAP3K5 |
0.16 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-94565 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 12391142 |
Coimmunoprecipitation analysis revealed a physical interaction between endogenous hsp72 and ask1 in nih 3t3 cells exposed to mild heat shock. Hsp72 blocked both the homo-oligomerization of ask1 and ask1-dependent apoptosis. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
TRAF2 | up-regulates activity
binding
|
MAP3K5 |
0.58 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-75334 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 10688666 |
Tnf receptor (tnfr) associated factor 2 (traf2), an adapter protein that couples tnfrs to the sapks and p38s, can activate ask1 in vivo and can interact in vivo with the amino- and carboxyl-terminal noncatalytic domains of the ask1 polypeptide |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-60747 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 9774977 |
Traf2 is a strong activator of ask1 |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | TNF alpha |
| + |
MAP3K5 | up-regulates
phosphorylation
|
MAP2K7 |
0.53 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-161766 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 19920149 |
Ask1 is a member of a mapkkk family and functions as an upstream kinase engaged in c-jun nh2-terminal kinase (jnk)/p38 signaling via the phosphorylation and activation of mapkks, such as mkk3, -4, -6, and -7 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-117264 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11959862 |
Activation of mkk7 by ask1 |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | TNF alpha |
| + |
MAP3K5 | up-regulates activity
phosphorylation
|
MAP2K6 |
0.64 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-45353 |
|
|
Homo sapiens |
COS-7 Cell |
| pmid |
sentence |
| 8974401 |
A MAP kinase kinase kinase (MAPKKK), termed ASK1, was identified that activated two different subgroups of MAP kinase kinases (MAPKK), SEK1 (or MKK4) and MKK3/MAPKK6 (or MKK6), which in turn activated stress-activated protein kinase (SAPK, also known as JNK; c-Jun amino-terminal kinase) and p38 subgroups of MAP kinases, respectively. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | P38 Signaling, P38 Signaling and Myogenesis |
| + |
DAXX | up-regulates
binding
|
MAP3K5 |
0.75 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-60164 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 9743501 |
Daxx was found to activate the jnk kinase kinase ask1, and overexpression of a kinase-deficient ask1 mutant inhibited fas- and daxx-induced apoptosis and jnk activation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
FAS | up-regulates
binding
|
MAP3K5 |
0.11 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-109676 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11495919 |
Ask1 binds fas |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SPAG9 |
binding
|
MAP3K5 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-235545 |
|
|
Mus musculus |
C2C12 Cell, Myoblast, HEK-293T Cell |
| pmid |
sentence |
| 22337877 |
Cdo and jlp interacted with ask1 or tak1 in 293t cells and c2c12 myoblasts |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | P38 Signaling and Myogenesis |
| + |
CDON/SPAG9 |
binding
|
MAP3K5 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-235557 |
|
|
Mus musculus |
C2C12 Cell, Myoblast, HEK-293T Cell |
| pmid |
sentence |
| 22337877 |
Cdo and jlp interacted with ask1 or tak1 in 293t cells and c2c12 myoblasts |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
RAF1 | down-regulates
binding
|
MAP3K5 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-109023 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11427728 |
Raf-1 interacts with the proapoptotic, stress-activated protein kinase ask1 (apoptosis signal-regulating kinase 1) in vitro and in vivo. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
DAB2IP | up-regulates activity
binding
|
MAP3K5 |
0.59 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-254748 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 27858941 |
DAB2IP also mediates recruitment of PP2A to ASK1, binding both proteins through its C2 domain; this favors removal of the inhibitory S967 phosphorylation and further activation of ASK1 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CDON |
binding
|
MAP3K5 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-235551 |
|
|
Mus musculus |
C2C12 Cell, Myoblast, HEK-293T Cell |
| pmid |
sentence |
| 22337877 |
Cdo and jlp interacted with ask1 or tak1 in 293t cells and c2c12 myoblasts |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | P38 Signaling and Myogenesis |
| + |
ROS | up-regulates
unknown
|
MAP3K5 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-226609 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11266364 |
TNF- but not Fas-induced apoptosis requires ROS-dependent activation of ASK1_JNK/p38 pathways. Thus, ASK1 is selectively required for TNF- and oxidative stress-induced sustained activations of JNK/p38 and apoptosis. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | P38 Signaling |
MAP3K5
- 
- 