| + |
BIRC2 | up-regulates activity 
ubiquitination, polyubiquitination
|
RIPK1 |
0.779 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-179100 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 18570872 |
CIAP1 and cIAP2 directly ubiquitinate RIP1 and induce constitutive RIP1 ubiquitination in cancer cells and demonstrate that constitutively ubiquitinated RIP1 associates with the prosurvival kinase TAK1. In this way RIP1 functions as a prosurvival scaffold molecule instead of a proapoptotic adaptor protein |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272710 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 21931591 |
CIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1-4).Together, our results demonstrate that depleting cIAP1/2 inhibits RIP1-4 mediated NF-kB activation without affecting RIP auto-phosphorylation. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-179439 |
|
|
Homo sapiens |
Fibrosarcoma Cell |
| pmid |
sentence |
| 18621737 |
c-IAPs are ubiquitin ligases capable of promoting polymerization of non-degradative Lys-63-linked polyubiquitin chains on the critical adapter in the canonical NF-_B signaling pathway, RIP1. c-IAPs are E3 ligases and RIP1 ubiquitination is critical for propagation of TNF_-induced NF-_B activation |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-145036 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16603398 |
In this report, we show that ciap1 and ciap2 promote cancer cell survival by functioning as e3 ubiquitin ligases that maintain constitutive ubiquitination of the rip1 adaptor protein. |
|
| Publications: |
4 |
Organism: |
Homo Sapiens |
| + |
NFKB1 | up-regulates quantity by expression 
transcriptional regulation
|
BIRC2 |
0.404 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-59948 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 9733516 |
Thus, our data indicate that nf-kb controls the expression of traf1 and traf2 and c-iap1 and c-iap2 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
BIRC2 | down-regulates quantity by destabilization 
polyubiquitination, ubiquitination
|
PACS2 |
0.298 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272851 |
|
|
in vitro |
|
| pmid |
sentence |
| 24633224 |
Under basal conditions, PACS-2 underwent K48-linked poly-ubiquitination, resulting in PACS-2 proteasomal degradation. Biochemical assays showed cIAP-1 and cIAP-2 interacted with PACS-2 in vitro and co-immunoprecipitation studies demonstrated that the two cIAPs bound PACS-2 in vivo. More importantly, both cIAP-1 and cIAP-2 directly mediated PACS-2 ubiquitination in a cell-free assay. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278743 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 24633224 |
The principal findings indicate that (i) PACS-2 is constitutively polyubiquitinated and degraded via the proteasome pathway in liver cells; (ii) Cellular Inhibitor of Apoptoses bind to and directly ubiquitinate PACS-2; (iii) pharmacological depletion (by SMAC mimetics) or genetic deletion of both cIAP-1 and cIAP-2 impairs PACS-2 ubiquitination and results in its intracellular accumulation; and (iv) PACS-2 accumulation facilitates its translocation to the lysosomes following TRAIL treatment, promoting TRAIL-induced lysosomal membrane permeabilization and apoptosis.|The principal findings indicate that (i) PACS-2 is constitutively polyubiquitinated and degraded via the proteasome pathway in liver cells; (ii) cIAPs bind to and directly ubiquitinate PACS-2; (iii) pharmacological depletion (by SMAC mimetics) or genetic deletion of both cIAP-1 and cIAP-2 impairs PACS-2 ubiquitination and results in its intracellular accumulation; and (iv) PACS-2 accumulation facilitates its translocation to the lysosomes following TRAIL treatment, promoting TRAIL induced LMP and apoptosis. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278742 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 24633224 |
The principal findings indicate that (i) PACS-2 is constitutively polyubiquitinated and degraded via the proteasome pathway in liver cells; (ii) Cellular Inhibitor of Apoptoses bind to and directly ubiquitinate PACS-2; (iii) pharmacological depletion (by SMAC mimetics) or genetic deletion of both cIAP-1 and cIAP-2 impairs PACS-2 ubiquitination and results in its intracellular accumulation; and (iv) PACS-2 accumulation facilitates its translocation to the lysosomes following TRAIL treatment, promoting TRAIL-induced lysosomal membrane permeabilization and apoptosis.|Therefore, it appears that cIAP-1 and cIAP-2 act coordinately and redundantly to ubiquitinate PACS-2. |
|
| Publications: |
3 |
Organism: |
In Vitro, Homo Sapiens |
| + |
BIRC2 | down-regulates quantity by destabilization
ubiquitination
|
TRAF2 |
0.877 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-182128 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 18997794 |
Traf3-binding receptors stabilize nik by activating ciap-dependent degradation of traf2 and traf3. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-167057 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20651737 |
Engagement of cd40 with its ligand cd40l results in the recruitment of the TRAF3/TRAF2/cIAP Complex to the receptor. At the receptor, traf3 undergoes ciap-dependent k48-linked polyubiquitylation (ub) that targets it for proteasomal degradation. In the absence of traf3, nik protein levels accumulate as it can no longer be recruited to the TRAF2/cIAP Complex. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | NF-KB Non Canonical |
| + |
DIABLO | down-regulates quantity
binding
|
BIRC2 |
0.899 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-80206 |
|
|
in vitro |
|
| pmid |
sentence |
| 10929711 |
Smac promotes caspase-9 activation by binding to inhibitor of apoptosis proteins, IAPs, and removing their inhibitory activity. Smac is normally a mitochondrial protein but is released into the cytosol when cells undergo apoptosis. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-121883 |
|
|
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 14960576 |
Smac/DIABLO selectively reduces the levels of c-IAP1 and c-IAP2 but not that of XIAP and livin in HeLa cells. |
|
| Publications: |
2 |
Organism: |
In Vitro, Homo Sapiens |
| + |
DIABLO | down-regulates activity
binding
|
BIRC2 |
0.899 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-80222 |
|
|
Homo sapiens |
HEK-293 Cell, NTERA-2 Cell |
| pmid |
sentence |
| 10929712 |
Diablo seem to function as a general iaps neutralizer by binding to these protein. Diablo promotes casp9 activation by binding to inhibitor of apoptosis proteins, iaps, and removing their inhibitory activity. ciap1 and ciap2 undergo autoubiquitination and degradation upon binding to the iap antagonist second mitochondrial activator of caspases (smac)/direct iap-binding protein with low pi (diablo), which is released from the mitochondria. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
BIRC2 | up-regulates activity
ubiquitination
|
ENDOG |
0.456 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278605 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 25139236 |
Alternatively, cIAP1 may mediate a vital function of EndoG other than cell death.|Cellular inhibitor of apoptosis protein 1 ubiquitinates endonuclease G but does not affect endonuclease G-mediated cell death. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
BIRC2 | down-regulates quantity by destabilization
ubiquitination
|
DIABLO |
0.899 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271392 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 12525502 |
Here we show that cIAP1 and cIAP2 are E3 ubiquitin-protein isopeptide ligases (ubiquitin ligases) for Smac. cIAPs stimulate Smac ubiquitination both in vivo and in vitro, leading to Smac degradation. cIAP1 and cIAP2 associate with overlapping but distinct subsets of E2 (ubiquitin carrier protein) ubiquitin-conjugating enzymes. The substrate-dependent E3 activity of cIAPs is mediated by their RING domains and is dependent on the specific interactions between cIAPs and Smac. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
TRADD | up-regulates activity
binding
|
BIRC2 |
0.711 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-45134 |
|
|
Homo sapiens |
HEK-293 Cell, U-937 Cell, HeLa Cell |
| pmid |
sentence |
| 8943045 |
The recruitment of TRAF2 and c-IAP1 to TNF-R1 is TNF-dependent, is mediated by TRADD. N-terminal domain of tradd may become accessible to traf2, thereby permitting recruitment of the traf2/ciap1 heterocomplex. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
BIRC2 | up-regulates activity
polyubiquitination
|
RIPK2 |
0.666 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272712 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 21931591 |
CIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1-4).Together, our results demonstrate that depleting cIAP1/2 inhibits RIP1-4 mediated NF-kB activation without affecting RIP auto-phosphorylation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
TRAF2 | up-regulates activity
binding
|
BIRC2 |
0.877 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-179449 |
|
|
Homo sapiens |
Fibrosarcoma Cell |
| pmid |
sentence |
| 18621737 |
Through its death domain and amino-terminal region, tradd recruits rip1 (receptor-interacting protein), traf2, and through its interaction with traf2, c-iap1 and c-iap2. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-39527 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 8548810 |
The c-iaps associate with traf1 and traf3 |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | NF-KB Non Canonical |
| + |
BIRC2 | down-regulates quantity by destabilization
polyubiquitination
|
CSE1L |
0.326 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272812 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 26668314 |
We find that TRAIL induces up-regulation of CAS in a posttranscriptional, caspase-8-dependent manner through degradation of cIAP1, an E3 ligase that targets CAS for ubiquitin-dependent proteasomal degradation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
BIRC2 | down-regulates quantity by destabilization
ubiquitination
|
EIF4E |
0.395 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278741 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 28852129 |
We found that endogenous eIF4E was ubiquitinated by cIAP1, and ubiquitinated eIF4E accumulated upon MG132 treatment. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
BIRC3 | up-regulates activity
binding
|
BIRC2 |
0.515 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-199088 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 23070005 |
Ligand-stimulated aggregation of receptor complexes causes recruitment of multiple traf2 trimers, which in turn leads to cIAP1 or cIAP2 dimerization. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
BIRC2 | down-regulates quantity
ubiquitination
|
CFLAR |
0.679 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278687 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 22345097 |
Moreover, API-1 increased c-FLIP ubiquitination and decreased c-FLIP stability.|Thus, we conclude that API-1 reduces c-FLIP levels by facilitating its degradation through the ubiquitin and proteasome dependent pathway. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
BIRC2 | down-regulates quantity by destabilization
ubiquitination
|
UBE2J1 |
0.361 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-263092 |
|
|
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 28321712 |
We also found that ubiquitin-ligase (E3), c-IAP1 preferentially interacts with phosphorylated Ube2j1. Moreover, we noticed that phosphorylated Ube2j1 is rapidly degraded by the proteasome during ER stress cell recovery. Taken together, these data suggest that Ube2j1 and its phosphorylation is important for transient ER stress cell recovery and the phosphorylated Ube2j1 is degraded by the proteasome. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SCF-FBW7 | down-regulates quantity by destabilization
ubiquitination
|
BIRC2 |
0.304 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271553 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 16510124 |
Since Fbxo7 is one component of the SCF complex, we tried to determine whether overexpression of Fbxo7 could promote cIAP1 ubiquitination in the hope to reveal functional aspects of the cIAP1–Fbxo7 interaction. cIAP1-Flag was co-expressed with or without Fbxo7 in 293T cells. In conclusion, our results show that overexpression of Fbxo7 promotes the ubiquitination of cIAP1. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
AT-406 | down-regulates
chemical inhibition
|
BIRC2 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-189954 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| Other |
|
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
BIRC2 | up-regulates activity
polyubiquitination
|
RIPK4 |
0.348 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272706 |
|
lys51 |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 21931591 |
CIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1-4).Together, our results demonstrate that depleting cIAP1/2 inhibits RIP1-4 mediated NF-kB activation without affecting RIP auto-phosphorylation.Lysine residues K51 and K145 of RIP4 are critical for cIAP1-mediated ubiquitination and NF-kB activation. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272708 |
|
lys145 |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 21931591 |
CIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1-4).Together, our results demonstrate that depleting cIAP1/2 inhibits RIP1-4 mediated NF-kB activation without affecting RIP auto-phosphorylation.Lysine residues K51 and K145 of RIP4 are critical for cIAP1-mediated ubiquitination and NF-kB activation. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
BIRC2 | down-regulates quantity by destabilization
polyubiquitination
|
RIPK1 |
0.779 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272638 |
|
|
Homo sapiens |
MDA-MB-231 Cell |
| pmid |
sentence |
| 18570872 |
In this report, we show that cIAP1 and cIAP2 promote cancer cell survival by functioning as E3 ubiquitin ligases that maintain constitutive ubiquitination of the RIP1 adaptor protein. We demonstrate that AEG40730, a compound modeled on BIR-binding tetrapeptides, binds to cIAP1 and cIAP2, facilitates their autoubiquitination and proteosomal degradation, and causes a dramatic reduction in RIP1 ubiquitination. We show that cIAP1 and cIAP2 directly ubiquitinate RIP1 and induce constitutive RIP1 ubiquitination in cancer cells and demonstrate that constitutively ubiquitinated RIP1 associates with the prosurvival kinase TAK1. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Ub:E2 | up-regulates activity
ubiquitination
|
BIRC2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271051 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 34199813 |
The ubiquitination process is mediated sequentially by three classes of enzymes consisting of a Ub-activating enzyme E1, a Ub-conjugating enzyme E2, and a Ub ligase E3. Ub is first activated by E1 in an adenosine 5′-triphosphate (ATP)-dependent manner t |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
XAF1 | down-regulates
binding
|
BIRC2 |
0.407 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-156843 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 17613533 |
Immunoprecipitation studies indicate that xaf1 binds to xiap,birc2,birc3. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NfKb-p65/p50 | up-regulates quantity by expression
transcriptional regulation
|
BIRC2 |
0.539 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-64100 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 9916987 |
The iaps have been shown to be induced by nf-kappab or v-rel in multiple cell lines and conversely, hiap1 and hiap2 have been shown to activate nf-kappab possibly forming a positive feed-back loop. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
BIRC2 | up-regulates activity
polyubiquitination
|
RIPK3 |
0.691 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272711 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 21931591 |
CIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1-4).Together, our results demonstrate that depleting cIAP1/2 inhibits RIP1-4 mediated NF-kB activation without affecting RIP auto-phosphorylation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
BIRC2 | down-regulates quantity by destabilization
ubiquitination
|
BIRC2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-121877 |
|
|
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 14960576 |
Ciap1 and ciap2 undergo autoubiquitination and degradation upon binding to the iap antagonist second mitochondrial activator of caspases (smac)/direct iap-binding protein with low pi (diablo), which is released from the mitochondria. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | NF-KB Non Canonical |
| + |
BIRC2 | down-regulates
binding
|
CASP2 |
0.487 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-146738 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16701639 |
However, among hiap1, hiap2 and xiap, only hiap2 binds and inhibits caspase-2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
BIRC2 | up-regulates activity
ubiquitination
|
E2F1 |
0.33 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278688 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 28542143 |
The ability of cIAP1 to promote wt E2F1 transcriptional activity was retained by all E2F1 mutants, except the K161R/164R mutant for which cIAP1 was completely inactive and the K185R whose basal transactivation activity was weakly enhanced by cIAP1 (XREF_FIG).|Here, we demonstrated that the E3-ubiquitin ligase cellular inhibitor of apoptosis 1 (cIAP1) increases E2F1 K63-poly-ubiquitination on the lysine residue 161/164 cluster, which is associated with the transcriptional factor stability and activity. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
4.0
BIRC2
- 
- 