TRAF3
UniProt ID: Q13114
Entrez ID: 7187
Protein name: TNF receptor-associated factor 3 (EC 2.3.2.27) (CD40 receptor-associated factor 1) (CRAF1) (CD40-binding protein) (CD40BP) (LMP1-associated protein 1) (LAP1) (RING-type E3 ubiquitin transferase TRAF3)
External links: UniprotKB HGNC RefSeq COSMIC
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FUNCTION: Cytoplasmic E3 ubiquitin ligase that regulates various signaling pathways, such as the NF-kappa-B, mitogen-activated protein kinase (MAPK) and interferon regulatory factor (IRF) pathways, and thus controls a lot of biological processes in both immune and non-immune cell types (PubMed:33148...
FUNCTION: Cytoplasmic E3 ubiquitin ligase that regulates various signaling pathways, such as the NF-kappa-B, mitogen-activated protein kinase (MAPK) and interferon regulatory factor (IRF) pathways, and thus controls a lot of biological processes in both immune and non-immune cell types (PubMed:33148796, PubMed:33608556). In TLR and RLR signaling pathways, acts as an E3 ubiquitin ligase promoting the synthesis of 'Lys-63'-linked polyubiquitin chains on several substrates such as ASC that lead to the activation of the type I interferon response or the inflammasome (PubMed:25847972, PubMed:27980081). Following the activation of certain TLRs such as TLR4, acts as a negative NF-kappa-B regulator, possibly to avoid unregulated inflammatory response, and its degradation via 'Lys-48'-linked polyubiquitination is required for MAPK activation and production of inflammatory cytokines. Alternatively, when TLR4 orchestrates bacterial expulsion, TRAF3 undergoes 'Lys-33'-linked polyubiquitination and subsequently binds to RALGDS, mobilizing the exocyst complex to rapidly expel intracellular bacteria back for clearance (PubMed:27438768). Acts also as a constitutive negative regulator of the alternative NF-kappa-B pathway, which controls B-cell survival and lymphoid organ development. Required for normal antibody isotype switching from IgM to IgG. Plays a role T-cell dependent immune responses. Down-regulates proteolytic processing of NFKB2, and thereby inhibits non-canonical activation of NF-kappa-B. Promotes ubiquitination and proteasomal degradation of MAP3K14. {ECO:0000269|PubMed:15084608, ECO:0000269|PubMed:15383523, ECO:0000269|PubMed:17991829, ECO:0000269|PubMed:19937093, ECO:0000269|PubMed:20097753, ECO:0000269|PubMed:20185819, ECO:0000269|PubMed:25847972, ECO:0000269|PubMed:27980081, ECO:0000269|PubMed:32562145, ECO:0000269|PubMed:33148796, ECO:0000269|PubMed:33608556, ECO:0000269|PubMed:34011520}.
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GO - Biological processes (BP):
apoptotic process [GO:0006915]; defense response to virus [GO:0051607]; negative regulation of NF-kappaB transcription factor activity [GO:0032088]; positive regulation of JNK cascade [GO:0046330]; protein K63-linked ubiquitination [GO:0070534]; regulation of apoptotic process [GO:0042981]; regulati...
apoptotic process [GO:0006915]; defense response to virus [GO:0051607]; negative regulation of NF-kappaB transcription factor activity [GO:0032088]; positive regulation of JNK cascade [GO:0046330]; protein K63-linked ubiquitination [GO:0070534]; regulation of apoptotic process [GO:0042981]; regulation of cytokine production [GO:0001817]; regulation of defense response to virus [GO:0050688]; regulation of I-kappaB kinase/NF-kappaB signaling [GO:0043122]; regulation of interferon-beta production [GO:0032648]; regulation of proteolysis [GO:0030162]; signal transduction [GO:0007165]; toll-like receptor signaling pathway [GO:0002224]; Toll signaling pathway [GO:0008063]; TRIF-dependent toll-like receptor signaling pathway [GO:0035666]; tumor necrosis factor-mediated signaling pathway [GO:0033209]; type I interferon signaling pathway [GO:0060337]
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GO - Molecular function (MF):
identical protein binding [GO:0042802]; protein kinase binding [GO:0019901]; protein phosphatase binding [GO:0019903]; thioesterase binding [GO:0031996]; tumor necrosis factor receptor binding [GO:0005164]; ubiquitin protein ligase binding [GO:0031625]; ubiquitin-protein transferase activity [GO:000...
identical protein binding [GO:0042802]; protein kinase binding [GO:0019901]; protein phosphatase binding [GO:0019903]; thioesterase binding [GO:0031996]; tumor necrosis factor receptor binding [GO:0005164]; ubiquitin protein ligase binding [GO:0031625]; ubiquitin-protein transferase activity [GO:0004842]; zinc ion binding [GO:0008270]
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GO - Cellular component (CC):
CD40 receptor complex [GO:0035631]; cytoplasmic side of plasma membrane [GO:0009898]; cytosol [GO:0005829]; endosome [GO:0005768]; mitochondrion [GO:0005739]; serine/threonine protein kinase complex [GO:1902554]; ubiquitin ligase complex [GO:0000151]...
CD40 receptor complex [GO:0035631]; cytoplasmic side of plasma membrane [GO:0009898]; cytosol [GO:0005829]; endosome [GO:0005768]; mitochondrion [GO:0005739]; serine/threonine protein kinase complex [GO:1902554]; ubiquitin ligase complex [GO:0000151]
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TRAF3
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*NOTE: the Kaplan plots were collected from OncoLnc