Target Interacting Protein Information

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Target General Information
Target Interacting Proteins
References
Target General Information  Top
Target ID T86552 Target Info
Target Name Tumor necrosis factor receptor type I (TNF-R1)
Synonyms p60; p55; Tumor necrosis factor-binding protein 1; Tumor necrosis factor receptor superfamily member 1A; Tumor necrosis factor receptor 1; TNFR1; TNFR-I; TNFAR; TNF-RI; TBPI; CD120a
Target Type Clinical trial Target
Gene Name TNFRSF1A
Biochemical Class Cytokine receptor
UniProt ID
TNR1A_HUMAN 
Target Interacting Proteins  Top
Acyltransferases [+] 1 Acyltransferases +
Interacting Protein Name TNF receptor-associated factor 2 (TRAF2) Interacting Protein Interacting Protein Info
UniProt ID
TRAF2_HUMAN 
Synonyms MGC:45012; TRAP; TRAP3
Evidence Score (E-score) 17 Experimental Evidences +
1 Affinity Capture-Western [1]
2 Affinity Capture-Western [2]
3 Affinity Capture-Western [3]
4 Affinity Capture-Western [4]
5 Affinity Capture-Western [5]
6 Affinity Capture-Western [6]
7 Affinity Capture-Western [7]
8 Affinity Capture-Western [8]
9 Affinity Capture-Western [9]
10 Affinity Capture-Western [10]
11 Affinity Capture-Western [11]
12 Affinity Capture-Western [12]
13 Affinity Capture-Western [13]
14 Affinity Capture-Western [14]
15 Affinity Capture-Western [15]
16 Affinity Capture-Western [16]
17 Co-localization [17]
Adapter proteins [+] 1 Adapter proteins +
Interacting Protein Name TNF receptor-associated factor 1 (TRAF1) Interacting Protein Interacting Protein Info
UniProt ID
TRAF1_HUMAN 
Synonyms EBI6; MGC:10353
Evidence Score (E-score) 2 Experimental Evidences +
1 Affinity Capture-Western [1]
2 Reconstituted Complex [18]
Kinases [+] 6 Kinases +
Interacting Target Name Receptor-interacting protein 1 (RIPK1) Clinical trial Target Interacting Protein Info
UniProt ID
RIPK1_HUMAN 
Synonyms RIP-1; RIP1; RIP; Receptor-interacting serine/threonine-protein kinase 1; Cell death protein RIP
Evidence Score (E-score) 20 Experimental Evidences +
1 Affinity Capture-MS [19]
2 Affinity Capture-Western [20]
3 Affinity Capture-Western [21]
4 Affinity Capture-Western [22]
5 Affinity Capture-Western [23]
6 Affinity Capture-Western [2]
7 Affinity Capture-Western [24]
8 Affinity Capture-Western [25]
9 Affinity Capture-Western [3]
10 Affinity Capture-Western [26]
11 Affinity Capture-Western [27]
12 Affinity Capture-Western [28]
13 Affinity Capture-Western [29]
14 Affinity Capture-Western [30]
15 Affinity Capture-Western [31]
16 Affinity Capture-Western [32]
17 Affinity Capture-Western [6]
18 Affinity Capture-Western [33]
19 Affinity Capture-Western [34]
20 Affinity Capture-Western [35]
Interacting Target Name Inhibitor of nuclear factor kappa-B kinase beta (IKKB) Clinical trial Target Interacting Protein Info
UniProt ID
IKKB_HUMAN 
Synonyms Nuclear factor NF-kappa-B inhibitor kinase beta; NFKBIKB; Inhibitory kappa B kinase b; Inhibitor of nuclear factor kappa-B kinase subunit beta; IKK-beta; IKKbeta; IKK-B; IKK-2; IKK2; IkBKB; I-kappa-B-kinase beta; IkappaB kinase beta; I-kappa-B kinase 2; IkappaB kinase 2
Evidence Score (E-score) 7 Experimental Evidences +
1 Affinity Capture-Western [8]
2 Affinity Capture-Western [29]
3 Affinity Capture-Western [36]
4 Affinity Capture-Western [31]
5 Biochemical Activity [37]
6 Co-localization [17]
7 Reconstituted Complex [36]
Interacting Target Name Janus kinase 2 (JAK-2) Successful Target Interacting Protein Info
UniProt ID
JAK2_HUMAN 
Synonyms Tyrosine-protein kinase JAK2
Evidence Score (E-score) 3 Experimental Evidences +
1 Affinity Capture-Western [38]
2 Affinity Capture-Western [39]
3 Reconstituted Complex [38]
Interacting Target Name Epidermal growth factor receptor (EGFR) Successful Target Interacting Protein Info
UniProt ID
EGFR_HUMAN 
Synonyms Epidermal growth factor receptor variant III; Proto-oncogene c-ErbB-1 variant III; Receptor tyrosine-protein kinase erbB-1 variant III; EGFR variant III; ERBB variant III; ERBB1 variant III; HER1 variant III
Evidence Score (E-score) 2 Experimental Evidences +
1 Protein-Fragment Complementation Assay [40]
2 Yeast two hybrid [41]
Interacting Target Name Janus kinase 1 (JAK-1) Successful Target Interacting Protein Info
UniProt ID
JAK1_HUMAN 
Synonyms Tyrosine-protein kinase JAK1; JAK1B; JAK1A
Evidence Score (E-score) 2 Experimental Evidences +
1 Affinity Capture-Western [42]
2 Reconstituted Complex [38]
Interacting Target Name Extracellular signal-regulated kinase 2 (ERK2) Clinical trial Target Interacting Protein Info
UniProt ID
MK01_HUMAN 
Synonyms PRKM2; PRKM1; P42-MAPK; P42 Mitogen-activated protein kinase; Mitogen-activated protein kinase 2; Mitogen-activated protein kinase 1; MAPK 2; MAPK 1; MAP kinase isoform p42; MAP kinase 2; MAP kinase 1; ERT1; ERK-2
Evidence Score (E-score) 2 Experimental Evidences +
1 Affinity Capture-Western [43]
2 Biochemical Activity [44]
Proteasome components [+] 1 Proteasome components +
Interacting Protein Name Tumor necrosis factor type 1 receptor-associated protein 2 (PSMD2) Interacting Protein Interacting Protein Info
UniProt ID
PSMD2_HUMAN 
Synonyms P97; RPN1; S2; TRAP2
Evidence Score (E-score) 3 Experimental Evidences +
1 Reconstituted Complex [45]
2 Yeast two hybrid [45]
3 Yeast two hybrid [46]
Other proteins [+] 4 Other proteins +
Interacting Protein Name TNFRSF1A-associated via death domain (TRADD) Interacting Protein Interacting Protein Info
UniProt ID
TRADD_HUMAN 
Synonyms Hs.89862
Evidence Score (E-score) 19 Experimental Evidences +
1 Affinity Capture-MS [19]
2 Affinity Capture-Western [47]
3 Affinity Capture-Western [25]
4 Affinity Capture-Western [48]
5 Affinity Capture-Western [49]
6 Affinity Capture-Western [36]
7 Affinity Capture-Western [6]
8 Affinity Capture-Western [7]
9 Affinity Capture-Western [8]
10 Affinity Capture-Western [34]
11 Affinity Capture-Western [11]
12 Affinity Capture-Western [50]
13 Affinity Capture-Western [51]
14 Affinity Capture-Western [52]
15 Affinity Capture-Western [53]
16 Affinity Capture-Western [1]
17 Affinity Capture-Western [14]
18 Affinity Capture-Western [54]
19 Yeast two hybrid [55]
Interacting Target Name Tumor necrosis factor (TNF) Successful Target Interacting Protein Info
UniProt ID
TNFA_HUMAN 
Synonyms Tumour necrosis factor alpha; Tumour necrosis factor; Tumor necrosis factor ligand superfamily member 2; Tumor necrosis factor; TNFSF2; TNF-alpha; TNFalpha; TNF-a; TNFA; TNF alpha; Cachectin
Evidence Score (E-score) 8 Experimental Evidences +
1 Affinity Capture-MS [19]
2 Affinity Capture-MS [56]
3 Affinity Capture-Western [57]
4 Co-localization [17]
5 Far Western [58]
6 Reconstituted Complex [59]
7 Reconstituted Complex [60]
8 Reconstituted Complex [61]
Interacting Target Name Lymphotoxin-alpha (LTA) Clinical trial Target Interacting Protein Info
UniProt ID
TNFB_HUMAN 
Synonyms Tumor necrosis factor ligand superfamily member 1; TNFSF1; TNF-beta; TNFB; LT-alpha
Evidence Score (E-score) 2 Experimental Evidences +
1 Co-crystal Structure [62]
2 Reconstituted Complex [59]
Interacting Target Name Apoptosis antigen ligand (CD178) Literature-reported Target Interacting Protein Info
UniProt ID
TNFL6_HUMAN 
Synonyms Tumor necrosis factor ligand superfamily member 6; TNFSF6; FasL; Fas ligand; FAS antigen ligand; CD95-L; CD95L; CD95 ligand; CD178 antigen; CD178; APTL; APT1LG1; Apoptosis antigen ligand
Evidence Score (E-score) 2 Experimental Evidences +
1 Affinity Capture-Western [57]
2 Co-purification [63]
References  Top
REF 1 TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways. Cell. 1996 Jan 26;84(2):299-308.
REF 2 De-ubiquitinating protease USP2a targets RIP1 and TRAF2 to mediate cell death by TNF. Cell Death Differ. 2012 May;19(5):891-9.
REF 3 USP8 suppresses death receptor-mediated apoptosis by enhancing FLIPL stability. Oncogene. 2017 Jan 26;36(4):458-470.
REF 4 TNF-alpha induces matrix metalloproteinase-9 expression in A549 cells: role of TNFR1/TRAF2/PKCalpha-dependent signaling pathways. J Cell Physiol. 2010 Aug;224(2):454-64.
REF 5 Brazilin selectively disrupts proximal IL-1 receptor signaling complex formation by targeting an IKK-upstream signaling components. Biochem Pharmacol. 2014 Jun 15;89(4):515-25.
REF 6 TNF-dependent recruitment of the protein kinase RIP to the TNF receptor-1 signaling complex. Immunity. 1996 Apr;4(4):387-96.
REF 7 IL-6 cytoprotection in hyperoxic acute lung injury occurs via suppressor of cytokine signaling-1-induced apoptosis signal-regulating kinase-1 degradation. Am J Respir Cell Mol Biol. 2009 Mar;40(3):314-24.
REF 8 Nonstructural 5A protein of hepatitis C virus modulates tumor necrosis factor alpha-stimulated nuclear factor kappa B activation. J Biol Chem. 2002 Apr 12;277(15):13122-8.
REF 9 TRAF2 must bind to cellular inhibitors of apoptosis for tumor necrosis factor (tnf) to efficiently activate nf-{kappa}b and to prevent tnf-induced apoptosis. J Biol Chem. 2009 Dec 18;284(51):35906-15.
REF 10 Novel anti-apoptotic mechanism of A20 through targeting ASK1 to suppress TNF-induced JNK activation. Cell Death Differ. 2010 Dec;17(12):1830-41.
REF 11 Competitive control of independent programs of tumor necrosis factor receptor-induced cell death by TRADD and RIP1. Mol Cell Biol. 2006 May;26(9):3505-13.
REF 12 IAP antagonists target cIAP1 to induce TNFalpha-dependent apoptosis. Cell. 2007 Nov 16;131(4):682-93.
REF 13 Celastrol-Induced Nur77 Interaction with TRAF2 Alleviates Inflammation by Promoting Mitochondrial Ubiquitination and Autophagy. Mol Cell. 2017 Apr 6;66(1):141-153.e6.
REF 14 The tumor necrosis factor receptor 2 signal transducers TRAF2 and c-IAP1 are components of the tumor necrosis factor receptor 1 signaling complex. Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):13973-8.
REF 15 Sequestration of TRAF2 into stress granules interrupts tumor necrosis factor signaling under stress conditions. Mol Cell Biol. 2005 Mar;25(6):2450-62.
REF 16 Syk-mediated tyrosine phosphorylation of mule promotes TNF-induced JNK activation and cell death. Oncogene. 2016 Apr 14;35(15):1988-95.
REF 17 Using an in situ proximity ligation assay to systematically profile endogenous protein-protein interactions in a pathway network. J Proteome Res. 2014 Dec 5;13(12):5339-46.
REF 18 The Epstein-Barr virus transforming protein LMP1 engages signaling proteins for the tumor necrosis factor receptor family. Cell. 1995 Feb 10;80(3):389-99.
REF 19 Architecture of the human interactome defines protein communities and disease networks. Nature. 2017 May 25;545(7655):505-509.
REF 20 RAIDD is a new 'death' adaptor molecule. Nature. 1997 Jan 2;385(6611):86-9.
REF 21 c-IAP1 and UbcH5 promote K11-linked polyubiquitination of RIP1 in TNF signalling. EMBO J. 2010 Dec 15;29(24):4198-209.
REF 22 Ubiquitin-associated domain-containing ubiquitin regulatory X (UBX) protein UBXN1 is a negative regulator of nuclear factor B (NF-B) signaling. J Biol Chem. 2015 Apr 17;290(16):10395-405.
REF 23 The Ripoptosome, a signaling platform that assembles in response to genotoxic stress and loss of IAPs. Mol Cell. 2011 Aug 5;43(3):432-48.
REF 24 CYLD deubiquitinates RIP1 in the TNF-induced necrosome to facilitate kinase activation and programmed necrosis. PLoS One. 2013 Oct 2;8(10):e76841.
REF 25 Linear ubiquitination is involved in the pathogenesis of optineurin-associated amyotrophic lateral sclerosis. Nat Commun. 2016 Aug 24;7:12547.
REF 26 Modulation of RIP1 ubiquitylation and distribution by MeBS to sensitize cancer cells to tumor necrosis factor -induced apoptosis. Cancer Sci. 2010 Nov;101(11):2425-9.
REF 27 Down-regulation of c-FLIP Enhances death of cancer cells by smac mimetic compound. Cancer Res. 2009 Oct 1;69(19):7729-38.
REF 28 S-Nitrosylation of cIAP1 Switches Cancer Cell Fate from TNF/TNFR1-Mediated Cell Survival to Cell Death. Cancer Res. 2018 Apr 15;78(8):1948-1957.
REF 29 Tautomycetin suppresses the TNFalpha/NF-kappaB pathway via inhibition of IKK activation. Int J Oncol. 2008 Nov;33(5):1027-35.
REF 30 Recruitment of A20 by the C-terminal domain of NEMO suppresses NF-B activation and autoinflammatory disease. Proc Natl Acad Sci U S A. 2016 Feb 9;113(6):1612-7.
REF 31 USP4 targets TAK1 to downregulate TNF-induced NF-B activation. Cell Death Differ. 2011 Oct;18(10):1547-60.
REF 32 Triad3A regulates ubiquitination and proteasomal degradation of RIP1 following disruption of Hsp90 binding. J Biol Chem. 2006 Nov 10;281(45):34592-600.
REF 33 De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-kappaB signalling. Nature. 2004 Aug 5;430(7000):694-9.
REF 34 Ubiquitin binding modulates IAP antagonist-stimulated proteasomal degradation of c-IAP1 and c-IAP2(1). Biochem J. 2009 Jan 1;417(1):149-60.
REF 35 Ubiquitin chain editing revealed by polyubiquitin linkage-specific antibodies. Cell. 2008 Aug 22;134(4):668-78.
REF 36 Phospho-SXXE/D motif mediated TNF receptor 1-TRADD death domain complex formation for T cell activation and migration. J Immunol. 2011 Aug 1;187(3):1289-97.
REF 37 Activation of the NF-kappaB pathway by caspase 8 and its homologs. Oncogene. 2000 Sep 14;19(39):4451-60.
REF 38 Induction of Jak/STAT signaling by activation of the type 1 TNF receptor. J Immunol. 1998 Mar 15;160(6):2742-50.
REF 39 Type 1 TNF receptor forms a complex with and uses Jak2 and c-Src to selectively engage signaling pathways that regulate transcription factor activity. J Immunol. 2008 Jul 15;181(2):1288-98.
REF 40 The mammalian-membrane two-hybrid assay (MaMTH) for probing membrane-protein interactions in human cells. Nat Methods. 2014 May;11(5):585-92.
REF 41 In silico prediction of physical protein interactions and characterization of interactome orphans. Nat Methods. 2015 Jan;12(1):79-84.
REF 42 Tumor necrosis factor alpha (TNF-alpha) activates Jak1/Stat3-Stat5B signaling through TNFR-1 in human B cells. Cell Growth Differ. 2002 Jan;13(1):13-8.
REF 43 Inflammatory protein sPLA(2)-IIA abrogates TNFalpha-induced apoptosis in human astroglioma cells: Crucial role of ERK. Biochim Biophys Acta. 2009 Dec;1793(12):1837-47.
REF 44 Heterogeneity in the phosphorylation of human death receptors by p42(mapk/erk2). Biochem Biophys Res Commun. 2001 Oct 26;288(2):313-20.
REF 45 A protein related to a proteasomal subunit binds to the intracellular domain of the p55 TNF receptor upstream to its 'death domain'. FEBS Lett. 1995 Jun 19;367(1):39-44.
REF 46 Two-hybrid cloning of a gene encoding TNF receptor-associated protein 2, a protein that interacts with the intracellular domain of the type 1 TNF receptor: identity with subunit 2 of the 26S protease. J Immunol. 1997 May 1;158(9):4252-9.
REF 47 Prevention of constitutive TNF receptor 1 signaling by silencer of death domains. Science. 1999 Jan 22;283(5401):543-6.
REF 48 AIP1/DAB2IP, a novel member of the Ras-GAP family, transduces TRAF2-induced ASK1-JNK activation. J Biol Chem. 2004 Oct 22;279(43):44955-65.
REF 49 The ectodermal dysplasia receptor activates the nuclear factor-kappaB, JNK, and cell death pathways and binds to ectodysplasin A. J Biol Chem. 2001 Jan 26;276(4):2668-77.
REF 50 SH3RF2 functions as an oncogene by mediating PAK4 protein stability. Carcinogenesis. 2014 Mar;35(3):624-34.
REF 51 A novel TLR2-triggered signalling crosstalk synergistically intensifies TNF-mediated IL-6 induction. J Cell Mol Med. 2014 Jul;18(7):1344-57.
REF 52 Inhibition of receptor internalization by monodansylcadaverine selectively blocks p55 tumor necrosis factor receptor death domain signaling. J Biol Chem. 1999 Apr 9;274(15):10203-12.
REF 53 The receptor for the cytotoxic ligand TRAIL. Science. 1997 Apr 4;276(5309):111-3.
REF 54 CLIPR-59 regulates TNF--induced apoptosis by controlling ubiquitination of RIP1. Cell Death Dis. 2012 Feb 2;3:e264.
REF 55 The TNF receptor 1-associated protein TRADD signals cell death and NF-kappa B activation. Cell. 1995 May 19;81(4):495-504.
REF 56 A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway. Nat Cell Biol. 2004 Feb;6(2):97-105.
REF 57 Recruitment of TNF receptor 1 to lipid rafts is essential for TNFalpha-mediated NF-kappaB activation. Immunity. 2003 May;18(5):655-64.
REF 58 Identification of a 60-kD tumor necrosis factor (TNF) receptor as the major signal transducing component in TNF responses. J Exp Med. 1990 Oct 1;172(4):1019-23.
REF 59 Production of lymphotoxin (LT alpha) and a soluble dimeric form of its receptor using the baculovirus expression system. J Immunol Methods. 1994 Jan 12;168(1):79-89.
REF 60 Insertion of foreign T cell epitopes in human tumor necrosis factor alpha with minimal effect on protein structure and biological activity. J Biol Chem. 2004 Aug 6;279(32):33593-600.
REF 61 Identification of tumor necrosis factor (TNF) amino acids crucial for binding to the murine p75 TNF receptor and construction of receptor-selective mutants. J Biol Chem. 2001 Oct 5;276(40):37426-30.
REF 62 Crystal structure of the soluble human 55 kd TNF receptor-human TNF beta complex: implications for TNF receptor activation. Cell. 1993 May 7;73(3):431-45.
REF 63 Cytoskeleton-mediated death receptor and ligand concentration in lipid rafts forms apoptosis-promoting clusters in cancer chemotherapy. J Biol Chem. 2005 Mar 25;280(12):11641-7.

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