TRAF3 (TNF receptor associated factor 3)

Gene

• Entrez ID: 7187
• Gene name: TNF receptor associated factor 3
• Gene symbol: TRAF3
• Synonyms: CAP-1, CAP1, CD40bp, CRAF1, IIAE5, LAP1, RNF118
• Chromosome: 14
• Chromosome location: 14q32.32
• Summary: The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins associate with, and mediate the signal transduction from, members of the TNF receptor (TNFR) superfamily. This protein participates in the signal transduction of CD40, a TNFR family member important for the activation of the immune response. This protein is found to be a critical component of the lymphotoxin-beta receptor (LTbetaR) signaling complex, which induces NF-kappaB activation and cell death initiated by LTbeta ligation. Epstein-Barr virus encoded latent infection membrane protein-1 (LMP1) can interact with this and several other members of the TRAF family, which may be essential for the oncogenic effects of LMP1. The protein also plays a role in the regulation of antiviral response. Mutations in this are associated with Encephalopathy, acute, infection-induced, herpes-specific 5. [provided by RefSeq, Jul 2020]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs143813189	C>T	Risk-factor, likely-benign	Coding sequence variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT006827	hsa-miR-32-5p	Luciferase reporter assay	22709905
MIRT028936	hsa-miR-26b-5p	Microarray	19088304
MIRT486126	hsa-miR-3191-3p	PAR-CLIP	23592263
MIRT486127	hsa-miR-8085	PAR-CLIP	23592263
MIRT486128	hsa-miR-6731-5p	PAR-CLIP	23592263
MIRT486129	hsa-miR-4707-3p	PAR-CLIP	23592263
MIRT486131	hsa-miR-6746-5p	PAR-CLIP	23592263
MIRT568690	hsa-miR-574-5p	PAR-CLIP	20371350
MIRT568690	hsa-miR-574-5p	HITS-CLIP	23824327
MIRT568691	hsa-miR-4455	PAR-CLIP	20371350
MIRT568691	hsa-miR-4455	HITS-CLIP	23824327
MIRT568692	hsa-miR-129-5p	PAR-CLIP	20371350
MIRT568692	hsa-miR-129-5p	HITS-CLIP	23824327
MIRT568693	hsa-miR-6867-5p	PAR-CLIP	20371350
MIRT568693	hsa-miR-6867-5p	HITS-CLIP	23824327
MIRT568694	hsa-miR-4694-5p	PAR-CLIP	20371350
MIRT568695	hsa-miR-4286	PAR-CLIP	20371350
MIRT568695	hsa-miR-4286	HITS-CLIP	23824327
MIRT568695	hsa-miR-4286	HITS-CLIP	28735896
MIRT568696	hsa-miR-662	PAR-CLIP	20371350
MIRT568696	hsa-miR-662	HITS-CLIP	23824327
MIRT733291	hsa-miR-3178	Immunohistochemistry, Luciferase reporter assay, Microarray, qRT-PCR, Western blot	27493095
MIRT733992	hsa-miR-34a-5p	PCR array	28097098
MIRT790313	hsa-miR-361-3p	HITS-CLIP	28735896
MIRT790335	hsa-miR-3679-3p	HITS-CLIP	28735896
MIRT790531	hsa-miR-4639-3p	HITS-CLIP	28735896
MIRT790748	hsa-miR-548e-5p	HITS-CLIP	28735896
MIRT790950	hsa-miR-6777-3p	HITS-CLIP	28735896
MIRT790978	hsa-miR-6805-5p	HITS-CLIP	28735896
MIRT791019	hsa-miR-6846-5p	HITS-CLIP	28735896
MIRT791023	hsa-miR-6848-5p	HITS-CLIP	28735896

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001817	Process	Regulation of cytokine production	ISS
GO:0002224	Process	Toll-like receptor signaling pathway	ISS
GO:0004842	Function	Ubiquitin-protein transferase activity	IBA	21873635
GO:0004842	Function	Ubiquitin-protein transferase activity	TAS
GO:0005164	Function	Tumor necrosis factor receptor binding	IBA	21873635
GO:0005164	Function	Tumor necrosis factor receptor binding	IPI	11728344
GO:0005515	Function	Protein binding	IPI	7527023, 10791955, 12005438, 12270937, 14743216, 15280356, 19419966, 19893624, 20080758, 20138174, 20174559, 20732415, 21903422, 23153539, 23333941, 23871208, 25241761, 27980081, 28514442, 30561431, 30833792, 31980649, 32296183, 32514408
GO:0005739	Component	Mitochondrion	IEA
GO:0005768	Component	Endosome	IEA
GO:0005829	Component	Cytosol	TAS
GO:0006915	Process	Apoptotic process	IEA
GO:0007165	Process	Signal transduction	TAS	7530216
GO:0008063	Process	Toll signaling pathway	IEA
GO:0008270	Function	Zinc ion binding	IEA
GO:0009898	Component	Cytoplasmic side of plasma membrane	IBA	21873635
GO:0009898	Component	Cytoplasmic side of plasma membrane	ISS
GO:0016579	Process	Protein deubiquitination	TAS
GO:0019901	Function	Protein kinase binding	IEA
GO:0019903	Function	Protein phosphatase binding	IPI	23871208
GO:0030162	Process	Regulation of proteolysis	IMP	20185819
GO:0031625	Function	Ubiquitin protein ligase binding	IBA	21873635
GO:0031625	Function	Ubiquitin protein ligase binding	IPI	11279055
GO:0031996	Function	Thioesterase binding	IPI	11279055
GO:0032088	Process	Negative regulation of NF-kappaB transcription factor activity	IBA	21873635
GO:0032088	Process	Negative regulation of NF-kappaB transcription factor activity	IMP	20185819
GO:0032648	Process	Regulation of interferon-beta production	ISS
GO:0033209	Process	Tumor necrosis factor-mediated signaling pathway	IBA	21873635
GO:0033209	Process	Tumor necrosis factor-mediated signaling pathway	IMP	20185819
GO:0033209	Process	Tumor necrosis factor-mediated signaling pathway	TAS
GO:0035631	Component	CD40 receptor complex	ISS
GO:0035666	Process	TRIF-dependent toll-like receptor signaling pathway	TAS
GO:0042802	Function	Identical protein binding	IPI	32296183
GO:0042981	Process	Regulation of apoptotic process	IEA
GO:0043122	Process	Regulation of I-kappaB kinase/NF-kappaB signaling	IBA	21873635
GO:0045087	Process	Innate immune response	IEA
GO:0046330	Process	Positive regulation of JNK cascade	IBA	21873635
GO:0050688	Process	Regulation of defense response to virus	ISS
GO:0070534	Process	Protein K63-linked ubiquitination	IBA	21873635
GO:0098802	Component	Plasma membrane signaling receptor complex	IBA	21873635

Other IDs

• MIM: 601896
• HGNC: 12033
• e!Ensembl: ENSG00000131323

Protein

• UniProt ID: Q13114
• Protein name: TNF receptor-associated factor 3 (EC 2.3.2.27) (CAP-1) (CD40 receptor-associated factor 1) (CRAF1) (CD40-binding protein) (CD40BP) (LMP1-associated protein 1) (LAP1) (RING-type E3 ubiquitin transferase TRAF3)
• Protein function: Regulates pathways leading to the activation of NF-kappa-B and MAP kinases, and plays a central role in the regulation of B-cell survival. Part of signaling pathways leading to the production of cytokines and interferon. Required for normal antibody isotype switching from IgM to IgG. Plays a role T-cell dependent immune responses. Plays a role in the regulation of antiviral responses. Is an essential constituent of several E3 ubiquitin-protein ligase complexes. May have E3 ubiquitin-protein ligase activity and promote 'Lys-63'-linked ubiquitination of target proteins. Inhibits activation of NF-kappa-B in response to LTBR stimulation. Inhibits TRAF2-mediated activation of NF-kappa-B. Down-regulates proteolytic processing of NFKB2, and thereby inhibits non-canonical activation of NF-kappa-B. Promotes ubiquitination and proteasomal degradation of MAP3K14.
• PDB: 1FLK, 1FLL, 1KZZ, 1L0A, 1RF3, 1ZMS, 2ECY, 2GKW
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF02176	zf-TRAF	136 → 192	TRAF-type zinc finger	Family
  PF02176	zf-TRAF	192 → 251	TRAF-type zinc finger	Family

• Sequence:

  MESSKKMDSPGALQTNPPLKLHTDRSAGTPVFVPEQGGYKEKFVKTVEDKYKCEKCHLVL
  CSPKQTECGHRFCESCMAALLSSSSPKCTACQESIVKDKVFKDNCCKREILALQIYCRNE
  SRGCAEQLMLGHLLVHLKNDCHFEELPCVRPDCKEKVLRKDLRDHVEKACKYREATCSHC
  KSQVPMIALQKHEDTDCPCVVVSCPHKCSVQTLLRSELSAHLSECVNAPSTCSFKRYGCV
  FQGTNQQIKAHEASSAVQHVNLLKEWSNSLEKKVSLLQNESVEKNKSIQSLHNQICSFEI
  EIERQKEMLRNNESKILHLQRVIDSQAEKLKELDKEIRPFRQNWEEADSMKSSVESLQNR
  VTELESVDKSAGQVARNTGLLESQLSRHDQMLSVHDIRLADMDLRFQVLETASYNGVLIW
  KIRDYKRRKQEAVMGKTLSLYSQPFYTGYFGYKMCARVYLNGDGMGKGTHLSLFFVIMRG
  EYDALLPWPFKQKVTLMLMDQGSSRRHLGDAFKPDPNSSSFKKPTGEMNIASGCPVFVAQ
  TVLENGTYIKDDTIFIKVIVDTSDLPDP

• Sequence length: 568