Identifiers
HUGO:TRAF2
TNF receptor associated factor 2
HUGO:TRAF2 hgnc_id:HGNC:12032 HGNC:12032 ENTREZ:7186 UNIPROT:Q12933
HUGO:TRAF2 HGNC:12032 ENTREZ:7186 UNIPROT:Q12933

Maps_Modules
HMC:AVOIDING_IMMUNE_DESTRUCTION
 Adaptive Immune Response   / TCR_SIGNALING 
HMC:TUMOR_PROMOTING_INFLAMMATION
HMC:ACTIVATING_INVASION_AND_METASTASIS
 Cancer Associated Fibroblasts   / INFLAMMATORY_SIGNALING_PATHWAYS 
HMC:RESISTING_CELL_DEATH
 Regulated Cell Death   / STARVATION_AUTOPHAGY 
 Regulated Cell Death   / DEATH_RECEPTOR_PATHWAYS 
 Regulated Cell Death   / FAS_RESPONSE 
 Regulated Cell Death   / TNF_RESPONSE 
 Regulated Cell Death   / TRAIL_RESPONSE 
 Regulated Cell Death   / ER_STRESS 
 Innate Immunity   / IMMUNOSTIMULATORY_CYTOKINE_PATHWAYS 
HMC:EVADING_GROWTH_SUPPRESSORS
 Survival   / MAPK 

References
PMID:17462996 PMID:19392652
PMID:21232017, PMID:21133840, PMID:18641653
TNF induces TRADD-dependent and RIPK1-dependent recruitment of TRAF2 to TNFR1.
TNFR2 interacts with TRAF2 and TRAF1.
PMID:24378531
TNF via TNFR2 ??induces??TRAF2??degradation.
PMID:23850759
PMID:15592525
TRAF proteins are recruited to the TRADD-TNFR1 complex. TRADD couples TNFR1 to TRAF2. TRAF2 directly interacts with TNFR2. ERN1 activation is likely to trigger binding and activation of TRAF2.
PMID:11274345

References
ad_re400( Adaptive Immune Response  ):
PMID:14660645, PMID:18264787, PMID:11460167
Activated TAK1 phosphorylates IKK-beta proteins
leading to activation of NF-??B downstream of HMGB1.
PMID:21232017, PMID:21133840, PMID:17301840
PMID:24958845, PMID:24699077
The LUBAC complex ubiquitinates NEMO, a subunit of the IKK complex downstream of TNF and upregulates IkBa degradetion.
PMID:11280761
VEGF signaling blocs TNF-?? induced activation of I??B kinase (IKK complex).This decreased IKK activation correlated with the inhibition of I??B?? phosphorylation and degradation of I??B?? and I??B?? in HPCs, and this inhibition is inhdependent or FLT1 and KDR

Maps_Modules
HMC:RESISTING_CELL_DEATH
 Regulated Cell Death   / STARVATION_AUTOPHAGY 
 Regulated Cell Death   / DEATH_RECEPTOR_PATHWAYS 
 Regulated Cell Death   / FAS_RESPONSE 
 Regulated Cell Death   / TNF_RESPONSE 
 Regulated Cell Death   / TRAIL_RESPONSE 

References
rc_re1326( Regulated Cell Death  ):
PMID:18292600
AIP1 recruits phosphatase PP2A to ASK1 in tumor necrosis factor-induced ASK1-JNK activation
PMID:10734135
PMID:8974401
PMID:15310755

References
in_re730( Innate Immunity  ):
PMID:24378531
TNF via TNFR2 ??induces??TRAF2??degradation.

References
su_mpk1_mpk1_re122( Survival  ):
TRAF proteins are recruited to the TRADD-TNFR1 complex. TRADD couples TNFR1 to TRAF2.
PMID:11274345
su_mpk1_mpk1_re124( Survival  ):
Upon ligand-induced TNFR1 trimerisation (not modelled) the TNFR1 death domain binds the death domain of the platform adapter protein TRADD. In contrast TNFR2 does not possess a death domain and instead binds directly to TRAF proteins (TRAF2).
su_mpk1_mpk1_re125( Survival  ):
ER stress lead to the oligomerisation and activation of mammalian Ire1p (ERN1). ERN1 activation is likely to trigger binding and activation of TRAF2.

1. TRAF2@Cytoplasm

1. TRAF2@Cytosol

1. TRAF2@INNATE_IMMUNE_CELL_Membrane

1. TRAF2@TNFRSF1 Receptor Complex

1. TRAF2@T_cell
2. TRAF2|​ubi@T_cell

1. TAK1*|​pho:​TNFRSF1B:​TRAF2@Cytoplasm
2. MAP3K1|​pho:​TNFRSF1B:​TRAF2@Cytoplasm
3. MAP3K5|​pho:​TNFRSF1B:​TRAF2@Cytoplasm
4. MAP3K2_3*|​pho:​TNFRSF1B:​TRAF2@Cytoplasm
5. RIPK1:​TAK1*|​pho:​TNFRSF1A:​TRADD:​TRAF2@Cytoplasm
6. MAP3K1|​pho:​RIPK1:​TNFRSF1A:​TRADD:​TRAF2@Cytoplasm
7. MAP3K5|​pho:​RIPK1:​TNFRSF1A:​TRADD:​TRAF2@Cytoplasm
8. MAP3K2_3*|​pho:​RIPK1:​TNFRSF1A:​TRADD:​TRAF2@Cytoplasm

1. TNF:​TNFR2*:​TRAF1:​TRAF2@Cytosol
2. FADD:​RIPK1:​TNF:​TNFR1*:​TRADD:​TRAF2@Cytosol
3. FADD:​RIPK1|​ubi:​TNF:​TNFR1*:​TRADD:​TRAF2|​ubi@Cytosol

1. MCL1|​pho|​hm2:​TRAF2:​Unfolded protein*@Endopasmic Reticulum

1. ASK1*:​CFLAR:​Caspase8,10*|​ubi:​DAXX:​FADD:​FAF1:​FASLG:​FAS|​pal:​FLASH*:​RIPK1|​emp|​K377_ubi:​TRAF2@Endosome

1. TNF:​TNFR2*:​TRAF1:​TRAF2@INNATE_IMMUNE_CELL_Membrane
2. FADD:​RIPK1:​TNF:​TNFR1*:​TRADD:​TRAF2@INNATE_IMMUNE_CELL_Membrane
3. FADD:​RIPK1|​ubi:​TNF:​TNFR1*:​TRADD:​TRAF2|​ubi@INNATE_IMMUNE_CELL_Membrane

1. ERN1:​TRAF2@Plasma Membrane
2. TNFRSF1B:​TRAF2@Plasma Membrane
3. TNFRSF1A:​TRADD:​TRAF2@Plasma Membrane
4. RIPK1:​TNFRSF1A:​TRADD:​TRAF2@Plasma Membrane

1. TRAF2@T_cell → TRAF2|​ubi@T_cell
2. TRAF2|​ubi@T_cell → degraded
3. TNF@default + TNFR1*@Cytosol + TRADD@Cytosol + TRAF2@Cytosol + RIPK1@Cytosol + FADD@Cytosol → FADD:​RIPK1:​TNF:​TNFR1*:​TRADD:​TRAF2@Cytosol
4. FADD:​RIPK1:​TNF:​TNFR1*:​TRADD:​TRAF2@Cytosol → FADD:​RIPK1|​ubi:​TNF:​TNFR1*:​TRADD:​TRAF2|​ubi@Cytosol
5. TNF@default + TNFR2*@Cytosol + TRAF2@Cytosol + TRAF1@Cytosol → TNF:​TNFR2*:​TRAF1:​TRAF2@Cytosol
6. FADD:​RIPK1:​TNF:​TNFR1*:​TRADD:​TRAF2@INNATE_IMMUNE_CELL_Membrane → FADD:​RIPK1|​ubi:​TNF:​TNFR1*:​TRADD:​TRAF2|​ubi@INNATE_IMMUNE_CELL_Membrane
7. TNF@default + TNFR1*@INNATE_IMMUNE_CELL_Membrane + TRADD@INNATE_IMMUNE_CELL_Membrane + TRAF2@INNATE_IMMUNE_CELL_Membrane + RIPK1@INNATE_IMMUNE_CELL_Membrane + FADD@INNATE_IMMUNE_CELL_Membrane → FADD:​RIPK1:​TNF:​TNFR1*:​TRADD:​TRAF2@INNATE_IMMUNE_CELL_Membrane
8. TNF@default + TNFR2*@INNATE_IMMUNE_CELL_Membrane + TRAF1@INNATE_IMMUNE_CELL_Membrane + TRAF2@INNATE_IMMUNE_CELL_Membrane → TNF:​TNFR2*:​TRAF1:​TRAF2@INNATE_IMMUNE_CELL_Membrane
9. TRAF2@INNATE_IMMUNE_CELL_Membrane → degraded
10. TRAF2@Cytosol → TRAF2@TNFRSF1 Receptor Complex
11. DAB2IP|​S604_pho@TNFRSF1 Receptor Complex + TRAF2@TNFRSF1 Receptor Complex + TRADD@TNFRSF1 Receptor Complex → rc_s4171
12. Caspase8,10*:​DR4/5*|​gly|​pal@Cytosol + TRAF2@Cytosol + IKBKG@Cytosol + TRADD@Cytosol + RIPK1@Cytosol → Caspase10*:​Caspase8*@Cytosol
13. CFLAR:​Caspase8,10*|​ubi:​FADD:​FAF1:​FASLG:​FAS|​pal:​FLASH*:​MLKL:​RIPK1|​emp|​S161_pho:​RIPK3|​S199_pho@Endosome → ASK1*:​CFLAR:​Caspase8,10*|​ubi:​DAXX:​FADD:​FAF1:​FASLG:​FAS|​pal:​FLASH*:​RIPK1|​emp|​K377_ubi:​TRAF2@Endosome
14. ASK1*:​CFLAR:​Caspase8,10*|​ubi:​DAXX:​FADD:​FAF1:​FASLG:​FAS|​pal:​FLASH*:​RIPK1|​emp|​K377_ubi:​TRAF2@Endosome → ASK1*@Cytosol
15. ASK1*:​CFLAR:​Caspase8,10*|​ubi:​DAXX:​FADD:​FAF1:​FASLG:​FAS|​pal:​FLASH*:​RIPK1|​emp|​K377_ubi:​TRAF2@Endosome → CFLAR:​Caspase8,10*|​ubi:​FADD:​FAF1:​FASLG:​FAS|​pal:​FLASH*:​MLKL:​RIPK1|​emp|​S161_pho:​RIPK3|​S199_pho@Endosome
16. ASK1*:​CFLAR:​Caspase8,10*|​ubi:​DAXX:​FADD:​FAF1:​FASLG:​FAS|​pal:​FLASH*:​RIPK1|​emp|​K377_ubi:​TRAF2@Endosome → Caspase8*|​ubi:​FLASH*@Cytosol
17. MCL1|​pho|​hm2:​TRAF2:​Unfolded protein*@Endopasmic Reticulum → mRNA translation@Cytosol
18. IRE1-alpha*:​Unfolded protein*@Endopasmic Reticulum + TRAF2@Cytosol → MCL1|​pho|​hm2:​TRAF2:​Unfolded protein*@Endopasmic Reticulum
19. MCL1|​pho|​hm2:​TRAF2:​Unfolded protein*@Endopasmic Reticulum → RIDD process@Cytosol
20. TRAF2@Cytosol → TRAF2@Cytosol
21. MCL1|​pho|​hm2:​TRAF2:​Unfolded protein*@Endopasmic Reticulum → RIDD process@Cytosol
22. MCL1|​pho|​hm2:​TRAF2:​Unfolded protein*@Endopasmic Reticulum → UPR@Cytosol
23. MCL1|​pho|​hm2:​TRAF2:​Unfolded protein*@Endopasmic Reticulum → adaptative response@Cytosol
24. TRAF2@Cytoplasm + TNFRSF1A:​TRADD@Plasma Membrane → TNFRSF1A:​TRADD:​TRAF2@Plasma Membrane
25. RIPK1@Cytoplasm + TNFRSF1A:​TRADD:​TRAF2@Plasma Membrane → RIPK1:​TNFRSF1A:​TRADD:​TRAF2@Plasma Membrane
26. TRAF2@Cytoplasm + TNFRSF1B@Plasma Membrane → TNFRSF1B:​TRAF2@Plasma Membrane
27. TRAF2@Cytoplasm + ERN1@Plasma Membrane → ERN1:​TRAF2@Plasma Membrane
28. RIPK1:​TNFRSF1A:​TRADD:​TRAF2@Plasma Membrane + TAK1*@Cytoplasm → RIPK1:​TAK1*|​pho:​TNFRSF1A:​TRADD:​TRAF2@Cytoplasm
29. TNFRSF1B:​TRAF2@Plasma Membrane + TAK1*@Cytoplasm → TAK1*|​pho:​TNFRSF1B:​TRAF2@Cytoplasm
30. MAP3K1@Cytoplasm + RIPK1:​TNFRSF1A:​TRADD:​TRAF2@Plasma Membrane → MAP3K1|​pho:​RIPK1:​TNFRSF1A:​TRADD:​TRAF2@Cytoplasm
31. MAP3K1@Cytoplasm + TNFRSF1B:​TRAF2@Plasma Membrane → MAP3K1|​pho:​TNFRSF1B:​TRAF2@Cytoplasm
32. MAP3K2_3*@Cytoplasm + RIPK1:​TNFRSF1A:​TRADD:​TRAF2@Plasma Membrane → MAP3K2_3*|​pho:​RIPK1:​TNFRSF1A:​TRADD:​TRAF2@Cytoplasm
33. MAP3K2_3*@Cytoplasm + TNFRSF1B:​TRAF2@Plasma Membrane → MAP3K2_3*|​pho:​TNFRSF1B:​TRAF2@Cytoplasm
34. TNFRSF1B:​TRAF2@Plasma Membrane → ROS@Cytoplasm
35. TNFRSF1A:​TRADD:​TRAF2@Plasma Membrane → ROS@Cytoplasm
36. RIPK1:​TNFRSF1A:​TRADD:​TRAF2@Plasma Membrane + MAP3K5@Cytoplasm → MAP3K5|​pho:​RIPK1:​TNFRSF1A:​TRADD:​TRAF2@Cytoplasm
37. TNFRSF1B:​TRAF2@Plasma Membrane + MAP3K5@Cytoplasm → MAP3K5|​pho:​TNFRSF1B:​TRAF2@Cytoplasm

1. IKBKG:​IKK_alpha_*:​IKK_beta_*@T_cell → IKBKG|​ubi:​IKK_alpha_*:​IKK_beta_*|​pho@T_cell
2. IKBKG:​IKK_alpha_*:​IKK_beta_*@Cytosol → IKBKG|​ubi:​IKK_alpha_*:​IKK_beta_*|​pho@Cytosol
3. MAP3K7@Cytosol + TAB2@Cytosol + TAB3@Cytosol → (MAP3K7:​TAB2:​TAB3)|​active@Cytosol
4. JNK*@Cytosol → JNK*|​pho|​active@Cytosol
5. ERK1/2*@Cytosol → ERK1/2*|​pho@Cytosol
6. MAP3K7@INNATE_IMMUNE_CELL_Cytosol + TAB2@INNATE_IMMUNE_CELL_Cytosol + TAB3@INNATE_IMMUNE_CELL_Cytosol → (MAP3K7:​TAB2:​TAB3)|​active@INNATE_IMMUNE_CELL_Cytosol
7. gIRF1@INNATE_IMMUNE_CELL_Cytosol → rIRF1@INNATE_IMMUNE_CELL_Cytosol
8. TRAF2@INNATE_IMMUNE_CELL_Membrane → degraded
9. IKBKG:​IKK_alpha_*:​IKK_beta_*@INNATE_IMMUNE_CELL_Cytosol → IKBKG|​ubi:​IKK_alpha_*:​IKK_beta_*|​pho@INNATE_IMMUNE_CELL_Cytosol
10. JNK*@INNATE_IMMUNE_CELL_Cytosol → JNK*|​pho|​active@INNATE_IMMUNE_CELL_Cytosol
11. p38*@INNATE_IMMUNE_CELL_Cytosol → p38*|​pho|​active@INNATE_IMMUNE_CELL_Cytosol
12. RIPK1@Cytosol → RIPK1@TNFRSF1 Receptor Complex
13. cIAP*@Cytosol → cIAP*@TNFRSF1 Receptor Complex
14. ruXBP1@Nucleus → rsXBP1@Nucleus
15. rIRE1-alpha*@Nucleus → rIRE1-alpha*@Nucleus
16. TRAF2@Cytosol → TRAF2@Cytosol
17. ASK1*@Cytosol → ASK1*|​pho|​active@Cytosol
18. CHUK:​IKBKB@Cytosol → CHUK:​SDHC|​pho|​pho@Cytosol
19. MAP2K4@Cytoplasm → MAP2K4|​pho|​pho@Cytoplasm
20. MAP2K3@Cytoplasm → MAP2K3|​pho|​pho@Cytoplasm
21. MAP2K7@Cytoplasm → MAP2K7|​pho|​pho@Cytoplasm
22. MAP2K6@Cytoplasm → MAP2K6|​pho|​pho@Cytoplasm
23. MEK*@Cytoplasm → MEK*|​pho|​pho@Cytoplasm