| + |
ITCH | down-regulates quantity by destabilization 
ubiquitination
|
MAVS |
0.631 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260362 |
Lys371 |
PTSMVLTkVSASTVP |
Homo sapiens |
HEK-293T Cell |
| pmid |
sentence |
| 19881509 |
These data collectively indicate that AIP4 is the E3 ligase for MAVS.|We generated single substitutions (K362A, K371A or K420A) and combined point substitutions of MAVS and tested their degradation. K371A or K420A MAVS showed partial resistance to PCBP2-induced degradation (data not shown), whereas MAVS with the combined substitutions K371A and K420A (KK-AA) completely withstood the degradation |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260363 |
Lys420 |
GLGSELSkPGVLASQ |
Homo sapiens |
HEK-293T Cell |
| pmid |
sentence |
| 19881509 |
These data collectively indicate that AIP4 is the E3 ligase for MAVS.|We generated single substitutions (K362A, K371A or K420A) and combined point substitutions of MAVS and tested their degradation. K371A or K420A MAVS showed partial resistance to PCBP2-induced degradation (data not shown), whereas MAVS with the combined substitutions K371A and K420A (KK-AA) completely withstood the degradation |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
ITCH | up-regulates activity 
polyubiquitination
|
H1-2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272926 |
Lys46 |
PVSELITkAVAASKE |
Homo sapiens |
MDA-MB-231 Cell |
| pmid |
sentence |
| 30517763 |
ITCH interacts with and ubiquitinates linker histone H1.2 at K46. ITCH biochemically competes with RNF168 and RNF8 to polyubiquitinate histone H1.2. The results indicated that ITCH-mediated K46-Ubn is essential for the binding of histone H1.2 to chromatin. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ATM | up-regulates activity
phosphorylation
|
ITCH |
0.267 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-276488 |
Ser162 |
TCSENGVsLCLPRLE |
Homo sapiens |
|
| pmid |
sentence |
| 23435430 |
Here we uncover ATM as a novel positive modulator of ITCH E3-ubiquitin ligase activity. A single residue on ITCH protein, S161, which is part of an ATM SQ consensus motif, is required for ATM-dependent activation of ITCH. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MAPK8 | up-regulates activity
phosphorylation
|
ITCH |
0.644 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-245323 |
Ser240 |
RRVSGNNsPSLSNGG |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 16446428 |
Itch undergoes JNK1-mediated phosphorylation that greatly enhances its enzymatic activity. To investigate how phosphorylation activates an E3 Ub ligase we have identified the JNK1 phosphorylation sites within Itch as S199, S232, and T222 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-249580 |
Ser273 |
RPASVNGsPSATSES |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 16446428 |
Itch undergoes JNK1-mediated phosphorylation that greatly enhances its enzymatic activity. To investigate how phosphorylation activates an E3 Ub ligase we have identified the JNK1 phosphorylation sites within Itch as S199, S232, and T222 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-249579 |
Thr263 |
PSRPPPPtPRRPASV |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 16446428 |
Itch undergoes JNK1-mediated phosphorylation that greatly enhances its enzymatic activity. To investigate how phosphorylation activates an E3 Ub ligase we have identified the JNK1 phosphorylation sites within Itch as S199, S232, and T222 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-245315 |
|
|
Mus musculus |
Helper T-lymphocyte |
| pmid |
sentence |
| 15358865 |
Activation of the Jun amino-terminal kinase (JNK) mitogen-activated protein kinase cascade after T cell stimulation accelerated degradation of c-Jun and JunB through phosphorylation-dependent activation of the E3 ligase Itch. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-245310 |
|
|
Mus musculus |
Hepatocyte |
| pmid |
sentence |
| 16469705 |
This is not due to direct c-FLIP phosphorylation but depends on JNK-mediated phosphorylation and activation of the E3 ubiquitin ligase Itch, |
|
| Publications: |
5 |
Organism: |
Homo Sapiens, Mus Musculus |
| + |
AKT1 | up-regulates quantity
phosphorylation
|
ITCH |
0.325 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272922 |
Ser257 |
PSRPPRPsRPPPPTP |
Homo sapiens |
MDA-MB-231 Cell |
| pmid |
sentence |
| 30517763 |
AKT1-mediated phosphorylation of ITCH at Ser257 drives its nuclear translocation |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
FYN | down-regulates activity
phosphorylation
|
ITCH |
0.373 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-245332 |
Tyr420 |
QFNQRFIyGNQDLFA |
Mus musculus |
Helper T-lymphocyte |
| pmid |
sentence |
| 16387660 |
Tyrosine phosphorylation of Itch appears to reduce its interaction with its substrate JunB. The turnover of JunB is accelerated in Fyn-deficient T cells, which is further reconstituted by Itch Tyr371 mutation |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
ITCH | down-regulates activity
ubiquitination
|
NFE2 |
0.423 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-275553 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 18718448 |
Itch regulates p45/NF-E2 in vivo by Lys63-linked ubiquitination| Interestingly, Itch suppressed the transactivation activity of p45/NF-E2 by adding a Lys63-linked polyubiquitin chain. Confocal microscopy revealed that ubiquitinated p45/NF-E2 became localized in the cytoplasm when Itch was over-expressed. Thus, Itch-mediated ubiquitination of p45/NF-E2 does not target the protein for proteasomal degradation, but instead retains p45/NF-E2 in the cytoplasm, where it cannot function as a transactivator. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ITCH | down-regulates
ubiquitination
|
NOTCH1 |
0.629 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-80702 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 10940313 |
Itch binds to the n-terminal portion of the notch intracellular domain via its ww domains and promotes ubiquitination of notch through its hect ubiquitin ligase domain. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Skin |
| + |
ITCH | up-regulates activity
binding
|
SPART |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261308 |
|
|
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 20719964 |
SPG20 Protein Spartin Is Recruited to Midbodies by ESCRT-III Protein Ist1 and Participates in Cytokinesis. Spartin colocalizes with Ist1 at the midbody, and depletion of Ist1 in cells significantly decreases the number of cells where spartin is present at midbodies. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CSK | down-regulates activity
phosphorylation
|
ITCH |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-245327 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 16888620 |
CISK strongly interacts and colocalizes with the E3 ubiquitin ligase AIP4, which is important for the ubiquitin-dependent lysosomal degradation of CXCR4. Moreover, the observed inhibition is both dependent on the interaction between CISK and AIP4 and on the activation status of CISK. Consistent with this, an activated form of CISK but not of the related kinase SGK1 phosphorylates specific sites of AIP4 in vitro. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ITCH | up-regulates
ubiquitination
|
SMAD2 |
0.464 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-128647 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15350225 |
Itch promotes ubiquitination of smad2 and augments smad2 phosphorylation that requires an intact ligase activity of itch. Moreover, itch facilitates complex formation between tgf-beta receptor and smad2 and enhances tgf-beta-induced transcription. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ITCH | down-regulates activity
ubiquitination
|
TRPV4 |
0.385 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272625 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 17110928 |
AIP4 ubiquitin ligase is involved in the ubiquitination of both TRPV4 and TRPC4.Ubiquitination of TRPV4 is dramatically increased by the HECT (homologous to E6-AP carboxyl terminus)-family ubiquitin ligase AIP4 without inducing degradation of this channel. Instead, AIP4 promotes the endocytosis of TRPV4 and decreases its amount at the plasma membrane. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ITCH | down-regulates
ubiquitination
|
GLI1 |
0.559 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-167838 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20818436 |
The consequent activation of_ itch, together with the recruitment of gli1 through direct binding with_ numb, allows gli1 to enter into the complex, resulting in gli1 ubiquitination and degradation. we demonstrate that the hedgehog transcription factor gli1 is targeted by numb for itch-dependent ubiquitination, which suppresses hedgehog signals, thus arresting growth and promoting cell differentiation |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-150847 |
|
|
Homo sapiens |
Brain Cancer Cell |
| pmid |
sentence |
| 17115028 |
The consequent activation of_ itch, together with the recruitment of gli1 through direct binding with_ numb, allows gli1 to enter into the complex, resulting in gli1 ubiquitination and degradation. we demonstrate that the hedgehog transcription factor gli1 is targeted by numb for itch-dependent ubiquitination, which suppresses hedgehog signals, thus arresting growth and promoting cell differentiation |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
ITCH | down-regulates quantity by destabilization
ubiquitination
|
BCL10 |
0.28 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271414 |
|
|
Homo sapiens |
JURKAT Cell |
| pmid |
sentence |
| 15082780 |
The HECT domain ubiquitin ligases NEDD4 and Itch promote ubiquitination and degradation of Bcl10, thus downmodulating NF-kappa B activation. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271413 |
|
|
Homo sapiens |
JURKAT Cell |
| pmid |
sentence |
| 15082780 |
The HECT domain ubiquitin ligases NEDD4 and Itch promote ubiquitination and degradation of Bcl10, thus downmodulating NF-kappa B activation. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
ITCH | down-regulates quantity
ubiquitination
|
CFLAR |
0.601 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-245307 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 16469705 |
Depends on JNK-mediated phosphorylation and activation of the E3 ubiquitin ligase Itch, which specifically ubiquitinates c-FLIP and induces its proteasomal degradation. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
ITCH | down-regulates
ubiquitination
|
NOTCH |
0.629 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-254331 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 10940313 |
Itch binds to the n-terminal portion of the notch intracellular domain via its ww domains and promotes ubiquitination of notch through its hect ubiquitin ligase domain. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Skin |
| + |
ITCH | up-regulates activity
binding
|
TNFAIP3 |
0.285 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-160621 |
|
|
Homo sapiens |
T-lymphocyte, Leukemia Cell |
| pmid |
sentence |
| 18246070 |
Here we demonstrate that the regulatory molecule tax1bp1 recruited the e3 ligase itch to a20 via two 'ppxy' motifs. Itch was essential for the termination of tumor necrosis factor receptor signaling by controlling a20-mediated recruitment and inactivation of rip1. (abstract) |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | IL1 Signaling , NF-KB Canonical |
| + |
ITCH | down-regulates quantity by destabilization
polyubiquitination
|
EGFR |
0.47 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272604 |
|
|
Chlorocebus aethiops |
COS-1 Cell |
| pmid |
sentence |
| 12226085 |
In summary, we have shown that CBLC and AIP4 can interact and that these two E3 ligases could contribute to down-regulate EGFR signaling by ubiquitination. |
|
| Publications: |
1 |
Organism: |
Chlorocebus Aethiops |
| + |
ITCH | down-regulates quantity by destabilization
polyubiquitination
|
LAPTM5 |
0.421 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272721 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 22009753 |
Here, we found that the level of LAPTM5 protein is regulated negatively by the degradation through ubiquitination by ITCH, an E3 ubiquitin ligase. ITCH directly binds to the PPxY motif of LAPTM5 via its WW domains and promotes ubiquitination through a HECT-type ligase domain. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ITCH | down-regulates
ubiquitination
|
SMAD7 |
0.52 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-137951 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15946939 |
We identified atrophin 1-interacting protein 4 (aip4) as an e3 ubiquitin ligase that specifically targets smad7 for ubiquitin-dependent degradation without affecting the turnover of the activated tbetari. Surprisingly, we found that despite the ability to degrade smad7, aip4 can inhibit tgf-beta signaling, presumably by enhancing the association of smad7 with the activated tbetari. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NUMB | up-regulates
binding
|
ITCH |
0.598 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-167844 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20818436 |
Numb activates the catalytic activity of itch, releasing it from an inhibitory intramolecular interaction between its homologous to e6-ap c-terminus and ww domains. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SPART | up-regulates activity
binding
|
ITCH |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261306 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 19580544 |
Cytosolic endogenous spartin is mono-ubiquitinated and we demonstrate that it interacts via a PPXY motif with the ubiquitin E3 ligases AIP4 [atrophin-interacting protein 4; ITCH (itchy E3 ubiquitin protein ligase homologue] [corrected] and AIP5 (WWP1). Surprisingly, the PPXY motif, AIP4 and AIP5 are not required for spartin's ubiquitination, and so we propose that spartin acts as an adaptor for these proteins. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ITCH | down-regulates quantity by destabilization
polyubiquitination, ubiquitination
|
ERBB4 |
0.589 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272618 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 17463226 |
Interaction with the ErbB-4 receptors occurs via the WW domains of AIP4/Itch. Functional analyses demonstrate that AIP4/Itch is recruited to the ErbB-4 receptor to promote its polyubiquitination and degradation, thereby regulating stability of the receptor and access of receptor intracellular domains to the nuclear compartment. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271416 |
|
|
Chlorocebus aethiops |
COS-7 Cell |
| pmid |
sentence |
| 18334649 |
Itch catalyzed ubiquitination of ErbB4 CYT-1, promoted its localization into intracellular vesicles, and stimulated degradation of ErbB4 CYT-1 |
|
| Publications: |
2 |
Organism: |
Homo Sapiens, Chlorocebus Aethiops |
| + |
RNF11 | up-regulates activity
binding
|
ITCH |
0.57 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-183188 |
|
|
Homo sapiens |
Breast Cancer Cell |
| pmid |
sentence |
| 19131965 |
Rnf11, together with tax1bp1 and itch, is an essential component of an a20 ubiquitin-editing protein complex; rnf11 is required for a20 to interact with and inactivate rip1 to inhibit tnf-mediated nf-_kb activation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | IL1 Signaling , NF-KB Canonical |
| + |
ITCH | down-regulates quantity by destabilization
ubiquitination
|
BID |
0.359 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271415 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 20392206 |
The ubiquitin ligase Itch mediates the antiapoptotic activity of epidermal growth factor by promoting the ubiquitylation and degradation of the truncated C-terminal portion of Bid |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ITCH | down-regulates quantity by destabilization
polyubiquitination
|
JUNB |
0.417 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272619 |
|
|
Mus musculus |
T-lymphocyte Cell Line |
| pmid |
sentence |
| 11828324 |
Itch promotes Ub conjugation to JunB Molecularly, Itch associated with and induced ubiquitination of JunB, a transcription factor that is involved in TH2 differentiation. However, in Itch−/− T cells under the same conditions, degradation of JunB was markedly delayed. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
ITCH | down-regulates
ubiquitination
|
DTX1 |
0.688 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-150002 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 17028573 |
Itch/aip4 mediates deltex degradation through the formation of k29-linked polyubiquitin chains. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MAPK8 | up-regulates
phosphorylation
|
ITCH |
0.644 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-144456 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16469705 |
Here we show that tnfalpha-mediated jnk activation accelerates turnover of the nf-kappab-induced antiapoptotic protein c-flip, an inhibitor of caspase-8. This is not due to direct c-flip phosphorylation but depends on jnk-mediated phosphorylation and activation of the e3 ubiquitin ligase itch, which specifically ubiquitinates c-flip and induces its proteasomal degradation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ITCH | down-regulates
ubiquitination
|
TNIP2 |
0.272 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-144453 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16469705 |
Here we show that tnfa-mediated jnk activation accelerates turnover of the NF-kappaBinduced antiapoptotic protein c-flip, an inhibitor of caspase-8. This is not due to direct c-flip phosphorylation but depends on jnk-mediated phosphorylation and activationof the e3ubiquitin ligaseitch, which speci?cally Ubiquitinates c-flip and induces its proteasomal degradation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ITCH | down-regulates activity
ubiquitination
|
TRPC4 |
0.356 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272624 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 17110928 |
Ubiquitination of TRPV4 is dramatically increased by the HECT (homologous to E6-AP carboxyl terminus)-family ubiquitin ligase AIP4 without inducing degradation of this channel. Instead, AIP4 promotes the endocytosis of TRPV4 and decreases its amount at the plasma membrane. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Ub:E2 | up-regulates activity
ubiquitination
|
ITCH |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271301 |
|
|
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 |
| + |
PCBP2 | up-regulates activity
binding
|
ITCH |
0.599 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260361 |
|
|
Homo sapiens |
HEK-293T Cell |
| pmid |
sentence |
| 19881509 |
Only AIP4 associated with PCBP2 and caused MAVS degradation. The interaction between PCBP2 and AIP4 was abrogated when the linker region or WB2 of PCBP2 was deleted, which confirmed our previous data indicating that this region was critical for PCBP2-mediated degradation of MAVS |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
3.0
ITCH
- 
- 