TRAF2 (TNF receptor associated factor 2)

Gene

• Entrez ID: 7186
• Gene name: TNF receptor associated factor 2
• Gene symbol: TRAF2
• Synonyms: MGC:45012, RNF117, TRAP, TRAP3
• Chromosome: 9
• Chromosome location: 9q34.3
• 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 superfamily. This protein directly interacts with TNF receptors, and forms a heterodimeric complex with TRAF1. This protein is required for TNF-alpha-mediated activation of MAPK8/JNK and NF-kappaB. The protein complex formed by this protein and TRAF1 interacts with the inhibitor-of-apoptosis proteins (IAPs), and functions as a mediator of the anti-apoptotic signals from TNF receptors. The interaction of this protein with TRADD, a TNF receptor associated apoptotic signal transducer, ensures the recruitment of IAPs for the direct inhibition of caspase activation. BIRC2/c-IAP1, an apoptosis inhibitor possessing ubiquitin ligase activity, can unbiquitinate and induce the degradation of this protein, and thus potentiate TNF-induced apoptosis. Multiple alternatively spliced transcript variants have been found for this gene, but the biological validity of only one transcript has been determined. [provided by RefSeq, Jul 2008]

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT437984	hsa-miR-502-5p	qRT-PCR, Luciferase reporter assay, Western blot	24677135
MIRT437984	hsa-miR-502-5p	Luciferase reporter assay	26861148
MIRT491336	hsa-miR-371a-5p	PAR-CLIP	23592263
MIRT491337	hsa-miR-4519	PAR-CLIP	23592263
MIRT491338	hsa-miR-3120-3p	PAR-CLIP	23592263
MIRT711855	hsa-miR-4279	HITS-CLIP	19536157
MIRT711856	hsa-miR-6851-3p	HITS-CLIP	19536157
MIRT711857	hsa-miR-6081	HITS-CLIP	19536157
MIRT711858	hsa-miR-6886-3p	HITS-CLIP	19536157
MIRT711859	hsa-miR-4722-5p	HITS-CLIP	19536157
MIRT711860	hsa-miR-5008-5p	HITS-CLIP	19536157
MIRT711861	hsa-miR-1976	HITS-CLIP	19536157
MIRT711862	hsa-miR-3653-5p	HITS-CLIP	19536157
MIRT711863	hsa-miR-4254	HITS-CLIP	19536157
MIRT711864	hsa-miR-3690	HITS-CLIP	19536157
MIRT711865	hsa-miR-5088-3p	HITS-CLIP	19536157
MIRT711866	hsa-miR-4530	HITS-CLIP	19536157
MIRT711867	hsa-miR-4459	HITS-CLIP	19536157
MIRT711868	hsa-miR-4695-5p	HITS-CLIP	19536157
MIRT711869	hsa-miR-6165	HITS-CLIP	19536157
MIRT733449	hsa-miR-892b	Immunoprecipitaion, Luciferase reporter assay, qRT-PCR, Western blot	26747895
MIRT734017	hsa-miR-34a-5p	PCR array	28097098

Transcription factors

Transcription factor	Regulation	Reference
NFKB1	Activation	15041463
NFKB1	Repression	15723831
NFKB1	Unknown	19392652
RELA	Activation	15041463
RELA	Repression	15723831
RELA	Unknown	19392652

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000151	Component	Ubiquitin ligase complex	IPI	17314283
GO:0002637	Process	Regulation of immunoglobulin production	IEA
GO:0002726	Process	Positive regulation of T cell cytokine production	IMP	15125833
GO:0002947	Component	Tumor necrosis factor receptor superfamily complex	IDA	23429285
GO:0004842	Function	Ubiquitin-protein transferase activity	IBA	21873635
GO:0004842	Function	Ubiquitin-protein transferase activity	IDA	15258597, 20577214
GO:0005164	Function	Tumor necrosis factor receptor binding	IBA	21873635
GO:0005164	Function	Tumor necrosis factor receptor binding	IPI	11279055, 11728344
GO:0005174	Function	CD40 receptor binding	ISS
GO:0005515	Function	Protein binding	IPI	8069916, 8565075, 8943045, 9020361, 9153189, 10075662, 10514511, 10521462, 10892748, 11278723, 11466612, 11777919, 11798190, 11907583, 14743216, 15121867, 16189514, 16282325, 16311516, 16611992, 16636664, 16713569, 17389591, 19332782, 19805025, 20447407, 20562859, 20676093, 21516116
GO:0005654	Component	Nucleoplasm	TAS
GO:0005829	Component	Cytosol	IDA
GO:0005829	Component	Cytosol	TAS
GO:0005938	Component	Cell cortex	IEA
GO:0006919	Process	Activation of cysteine-type endopeptidase activity involved in apoptotic process	TAS
GO:0007165	Process	Signal transduction	TAS	8702708
GO:0007249	Process	I-kappaB kinase/NF-kappaB signaling	TAS
GO:0007250	Process	Activation of NF-kappaB-inducing kinase activity	IMP	15125833
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:0010803	Process	Regulation of tumor necrosis factor-mediated signaling pathway	TAS
GO:0012506	Component	Vesicle membrane	IEA
GO:0016579	Process	Protein deubiquitination	TAS
GO:0019899	Function	Enzyme binding	IPI	16636664
GO:0019901	Function	Protein kinase binding	IPI	10650002
GO:0019903	Function	Protein phosphatase binding	IPI	15696169
GO:0030163	Process	Protein catabolic process	IEA
GO:0030674	Function	Protein-macromolecule adaptor activity	IPI	20447407
GO:0031435	Function	Mitogen-activated protein kinase kinase kinase binding	IEA
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:0032743	Process	Positive regulation of interleukin-2 production	IMP	15125833
GO:0033209	Process	Tumor necrosis factor-mediated signaling pathway	IBA	21873635
GO:0033209	Process	Tumor necrosis factor-mediated signaling pathway	IDA	11907583
GO:0033209	Process	Tumor necrosis factor-mediated signaling pathway	TAS
GO:0034351	Process	Negative regulation of glial cell apoptotic process	IEA
GO:0034622	Process	Cellular protein-containing complex assembly	ISS
GO:0034976	Process	Response to endoplasmic reticulum stress	NAS	10650002
GO:0035631	Component	CD40 receptor complex	ISS
GO:0042802	Function	Identical protein binding	IPI	8069916, 9020361, 16189514, 20562859, 25416956, 30561431, 31515488, 32296183
GO:0042981	Process	Regulation of apoptotic process	IDA	11907583
GO:0043120	Function	Tumor necrosis factor binding	IPI	23429285
GO:0043122	Process	Regulation of I-kappaB kinase/NF-kappaB signaling	IBA	21873635
GO:0043123	Process	Positive regulation of I-kappaB kinase/NF-kappaB signaling	IBA	21873635
GO:0043254	Process	Regulation of protein-containing complex assembly	IMP	11278723
GO:0043507	Process	Positive regulation of JUN kinase activity	IDA	11907583
GO:0044877	Function	Protein-containing complex binding	IEA
GO:0045121	Component	Membrane raft	IEA
GO:0046330	Process	Positive regulation of JNK cascade	IBA	21873635
GO:0046625	Function	Sphingolipid binding	IDA	20577214
GO:0051091	Process	Positive regulation of DNA-binding transcription factor activity	IMP	12296995
GO:0051092	Process	Positive regulation of NF-kappaB transcription factor activity	IDA	11279055
GO:0051092	Process	Positive regulation of NF-kappaB transcription factor activity	IMP	12296995, 15121867
GO:0051865	Process	Protein autoubiquitination	IDA	20577214
GO:0051865	Process	Protein autoubiquitination	TAS	16378096
GO:0065003	Process	Protein-containing complex assembly	TAS	8702708
GO:0070059	Process	Intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	TAS	14685163, 22013210
GO:0070534	Process	Protein K63-linked ubiquitination	IBA	21873635
GO:0070534	Process	Protein K63-linked ubiquitination	IDA	15258597, 20577214
GO:0071550	Process	Death-inducing signaling complex assembly	TAS
GO:0071732	Process	Cellular response to nitric oxide	IEA
GO:0097057	Component	TRAF2-GSTP1 complex	IDA	16636664
GO:0097300	Process	Programmed necrotic cell death	IEA
GO:0098802	Component	Plasma membrane signaling receptor complex	IBA	21873635
GO:1901215	Process	Negative regulation of neuron death	TAS	18221368
GO:1902041	Process	Regulation of extrinsic apoptotic signaling pathway via death domain receptors	TAS
GO:1902042	Process	Negative regulation of extrinsic apoptotic signaling pathway via death domain receptors	TAS
GO:1903265	Process	Positive regulation of tumor necrosis factor-mediated signaling pathway	IEA
GO:1903721	Process	Positive regulation of I-kappaB phosphorylation	IEA
GO:1990604	Component	IRE1-TRAF2-ASK1 complex	IDA	23000344
GO:2001238	Process	Positive regulation of extrinsic apoptotic signaling pathway	IMP	21525013

Other IDs

• MIM: 601895
• HGNC: 12032
• e!Ensembl: ENSG00000127191

Protein

• UniProt ID: Q12933
• Protein name: TNF receptor-associated factor 2 (EC 2.3.2.27) (E3 ubiquitin-protein ligase TRAF2) (RING-type E3 ubiquitin transferase TRAF2) (Tumor necrosis factor type 2 receptor-associated protein 3)
• Protein function: Regulates activation of NF-kappa-B and JNK and plays a central role in the regulation of cell survival and apoptosis. Required for normal antibody isotype switching from IgM to IgG. Has E3 ubiquitin-protein ligase activity and promotes 'Lys-63'-linked ubiquitination of target proteins, such as BIRC3, RIPK1 and TICAM1. Is an essential constituent of several E3 ubiquitin-protein ligase complexes, where it promotes the ubiquitination of target proteins by bringing them into contact with other E3 ubiquitin ligases. Regulates BIRC2 and BIRC3 protein levels by inhibiting their autoubiquitination and subsequent degradation; this does not depend on the TRAF2 RING-type zinc finger domain. Plays a role in mediating activation of NF-kappa-B by EIF2AK2/PKR. In complex with BIRC2 or BIRC3, promotes ubiquitination of IKBKE.
• PDB: 1CA4, 1CA9, 1CZY, 1CZZ, 1D00, 1D01, 1D0A, 1D0J, 1F3V, 1QSC, 3KNV, 3M06, 3M0A, 3M0D
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00097	zf-C3HC4	34 → 72	Zinc finger, C3HC4 type (RING finger)	Domain
  PF02176	zf-TRAF	178 → 235	TRAF-type zinc finger	Family
  PF16673	TRAF_BIRC3_bd	267 → 330	TNF receptor-associated factor BIRC3 binding domain	Coiled-coil

• Sequence:

  MAAASVTPPGSLELLQPGFSKTLLGTKLEAKYLCSACRNVLRRPFQAQCGHRYCSFCLAS
  ILSSGPQNCAACVHEGIYEEGISILESSSAFPDNAARREVESLPAVCPSDGCTWKGTLKE
  YESCHEGRCPLMLTECPACKGLVRLGEKERHLEHECPERSLSCRHCRAPCCGADVKAHHE
  VCPKFPLTCDGCGKKKIPREKFQDHVKTCGKCRVPCRFHAIGCLETVEGEKQQEHEVQWL
  REHLAMLLSSVLEAKPLLGDQSHAGSELLQRCESLEKKTATFENIVCVLNREVERVAMTA
  EACSRQHRLDQDKIEALSSKVQQLERSIGLKDLAMADLEQKVLEMEASTYDGVFIWKISD
  FARKRQEAVAGRIPAIFSPAFYTSRYGYKMCLRIYLNGDGTGRGTHLSLFFVVMKGPNDA
  LLRWPFNQKVTLMLLDQNNREHVIDAFRPDVTSSSFQRPVNDMNIASGCPLFCPVSKMEA
  KNSYVRDDAIFIKAIVDLTGL

• Sequence length: 501