| + |
RNF2 | down-regulates quantity by destabilization 
ubiquitination
|
AMBRA1 |
0.36 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278596 |
Lys45 |
RWMKWEGkRVELPDS |
Homo sapiens |
|
| pmid |
sentence |
| 24980959 |
RNF2 ubiquitinates AMBRA1 at lysine 45.|These data indicate that RNF2 directly accelerates the degradation of AMBRA1. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CHUK | up-regulates activity 
phosphorylation
|
AMBRA1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272974 |
Ser1043 |
CRPEALNsGVEYYWD |
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 30217973 |
Furthermore, we show that mitophagy function of AMBRA1 is post-translationally controlled, upon HUWE1 activity, by a positive phosphorylation on its serine 1014. This modification is mediated by the IKKα kinase and induces structural changes in AMBRA1, thus promoting its interaction with LC3/GABARAP (mATG8) proteins and its mitophagic activity. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CyclinB/CDK1 | up-regulates activity
phosphorylation
|
AMBRA1 |
0.257 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272969 |
Ser1252 |
QPTLPSSsPVPIPVS |
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 37584777 |
CDK1 phosphorylates AMBRA1 at T1209 and S1223. |CDK1-mediated phosphorylation primes PLK1 phosphorylation on AMBRA1|In this work, we show that AMBRA1 is sequentially phosphorylated at mitosis by CDK1 and PLK1 on multiple sites. In particular, CDK1 is responsible for the early phosphorylations on T1209 and S1223, and it promotes additional late phosphorylation events by PLK1 on AMBRA1. Altogether, these phosphorylation events are critical for proper spindle function and orientation. Indeed, phosphorylated AMBRA1 can interact with NUMA1 and is responsible for NUMA1 proper localization at the cell cortex. Moreover, we observe that loss of AMBRA1 leads to PLK1 protein stabilization and to an increase in phospho-NUMA1 levels which, in turn, contributes to spindle orientation defects. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272967 |
Thr1238 |
ASWDQPGtPGREPTQ |
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 37584777 |
CDK1 phosphorylates AMBRA1 at T1209 and S1223. |CDK1-mediated phosphorylation primes PLK1 phosphorylation on AMBRA1|In this work, we show that AMBRA1 is sequentially phosphorylated at mitosis by CDK1 and PLK1 on multiple sites. In particular, CDK1 is responsible for the early phosphorylations on T1209 and S1223, and it promotes additional late phosphorylation events by PLK1 on AMBRA1. Altogether, these phosphorylation events are critical for proper spindle function and orientation. Indeed, phosphorylated AMBRA1 can interact with NUMA1 and is responsible for NUMA1 proper localization at the cell cortex. Moreover, we observe that loss of AMBRA1 leads to PLK1 protein stabilization and to an increase in phospho-NUMA1 levels which, in turn, contributes to spindle orientation defects. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
CDK1 | up-regulates activity
phosphorylation
|
AMBRA1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272968 |
Ser1252 |
QPTLPSSsPVPIPVS |
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 37584777 |
CDK1 phosphorylates AMBRA1 at T1209 and S1223. |CDK1-mediated phosphorylation primes PLK1 phosphorylation on AMBRA1|In this work, we show that AMBRA1 is sequentially phosphorylated at mitosis by CDK1 and PLK1 on multiple sites. In particular, CDK1 is responsible for the early phosphorylations on T1209 and S1223, and it promotes additional late phosphorylation events by PLK1 on AMBRA1. Altogether, these phosphorylation events are critical for proper spindle function and orientation. Indeed, phosphorylated AMBRA1 can interact with NUMA1 and is responsible for NUMA1 proper localization at the cell cortex. Moreover, we observe that loss of AMBRA1 leads to PLK1 protein stabilization and to an increase in phospho-NUMA1 levels which, in turn, contributes to spindle orientation defects. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272966 |
Thr1238 |
ASWDQPGtPGREPTQ |
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 37584777 |
CDK1 phosphorylates AMBRA1 at T1209 and S1223. |CDK1-mediated phosphorylation primes PLK1 phosphorylation on AMBRA1|In this work, we show that AMBRA1 is sequentially phosphorylated at mitosis by CDK1 and PLK1 on multiple sites. In particular, CDK1 is responsible for the early phosphorylations on T1209 and S1223, and it promotes additional late phosphorylation events by PLK1 on AMBRA1. Altogether, these phosphorylation events are critical for proper spindle function and orientation. Indeed, phosphorylated AMBRA1 can interact with NUMA1 and is responsible for NUMA1 proper localization at the cell cortex. Moreover, we observe that loss of AMBRA1 leads to PLK1 protein stabilization and to an increase in phospho-NUMA1 levels which, in turn, contributes to spindle orientation defects. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
MTOR | down-regulates activity
phosphorylation
|
AMBRA1 |
0.471 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272986 |
Ser52 |
KRVELPDsPRSTFLL |
|
|
| pmid |
sentence |
| 23524951 |
We show that under non-autophagic conditions, mTOR inhibits AMBRA1 by phosphorylation, whereas on autophagy induction, AMBRA1 is dephosphorylated. In this condition, AMBRA1, interacting with the E3-ligase TRAF6, supports ULK1 ubiquitylation by LYS-63-linked chains, and its subsequent stabilization, self-association and function. As ULK1 has been shown to activate AMBRA1 by phosphorylation, the proposed pathway may act as a positive regulation loop, which may be targeted in human disorders linked to impaired autophagy.|mTOR phosphorylates AMBRA1 at Ser 52, inhibiting its role in ULK1 modification |
|
| Publications: |
1 |
| + |
AMBRA1 | up-regulates activity
binding
|
TRAF6 |
0.587 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272963 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 23524951 |
In this condition, AMBRA1, interacting with the E3-ligase TRAF6, supports ULK1 ubiquitylation by LYS-63-linked chains, and its subsequent stabilization, self-association and function. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
AMBRA1 | up-regulates activity
binding
|
BECN1 |
0.783 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-168252 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20921139 |
we show that the BECLIN 1-VPS34 complex is tethered to the cytoskeleton through an interaction between the BECLIN 1-interacting protein AMBRA1 and dynein light chains 1/2. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-156409 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 17589504 |
Here we show that Ambra1 (activating molecule in Beclin1-regulated autophagy), a large, previously unknown protein bearing a WD40 domain at its amino terminus, regulates autophagy and has a crucial role in embryogenesis. We found that Ambra1 is a positive regulator of the Becn1-dependent programme of autophagy |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Tissue: |
Fibrosarcoma Cell |
| Pathways: | Autophagy |
| + |
DYNLL1 | down-regulates
binding
|
AMBRA1 |
0.551 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-168255 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20921139 |
The beclin 1vps34 complex is tethered to the cytoskeleton through an interaction between the beclin 1interacting protein ambra1 and dynein light chains 1/2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
DYNLL2 | down-regulates
binding
|
AMBRA1 |
0.463 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-168289 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20921139 |
The beclin 1 vps34 complex is tethered to the cytoskeleton through an interaction between the beclin 1 interacting protein ambra1 and dynein light chains 1/2 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ULK1 | up-regulates
phosphorylation
|
AMBRA1 |
0.693 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-168292 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20921139 |
When autophagy is induced, ulk1 phosphorylates ambra1, releasing the autophagy core complex from dynein. Its subsequent relocalization to the endoplasmic reticulum enables autophagosome nucleation. Ambra1-dlc1 dissociates from the dynein complex upon ulk1-dependent ambra1 phosphorylation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
AMBRA1 | up-regulates activity
binding
|
PPP2CB |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272964 |
|
|
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 25438055 |
We found that AMBRA1 favours the interaction between c-Myc and its phosphatase PP2A and that, when mTOR is inhibited, it enhances PP2A activity on this specific target, thereby reducing the cell division rate. As expected, such a de-regulation of c-Myc correlates with increased tumorigenesis in AMBRA1-defective systems, thus supporting a role for AMBRA1 as a haploinsufficient tumour suppressor gene. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
AMBRA1 | up-regulates activity
relocalization
|
HUWE1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272962 |
|
|
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 30217973 |
AMBRA1 regulates mitophagy at two critical steps. Upon mitophagy stimulation, AMBRA1 mediates the HUWE1 E3 ubiquitin ligase translocation from cytosol to mitochondria (light blue). AMBRA1 acts as a cofactor for HUWE1 E3 ubiquitin ligase activity, favouring its binding to its substrate MFN2 (and maybe other OMM substrates) and targeting it to the proteasome |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ULK1/Atg13/Fip200 | up-regulates activity
phosphorylation
|
AMBRA1 |
0.665 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-219388 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 20921139 |
When autophagy is induced, ulk1 phosphorylates ambra1, releasing the autophagy core complex from dynein. Its subsequent relocalization to the endoplasmic reticulum enables autophagosome nucleation. Ambra1-dlc1 dissociates from the dynein complex upon ulk1-dependent ambra1 phosphorylation. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Autophagy |
4.0
AMBRA1
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