TRAF2 TNF receptor associated factor 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: TRAF2provided by HGNC
Official Full Name: TNF receptor associated factor 2provided by HGNC
Primary source: HGNC:HGNC:12032
See related: Ensembl:ENSG00000127191 MIM:601895; AllianceGenome:HGNC:12032
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: TRAP; TRAP3; RNF117; MGC:45012
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]
Expression: Ubiquitous expression in lymph node (RPKM 3.4), spleen (RPKM 3.0) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 9q34.3

Exon count:: 17

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	9	NC_000009.12 (136881958..136926607)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	9	NC_060933.1 (149116134..149160997)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	9	NC_000009.11 (139780968..139821059)

Chromosome 9 - NC_000009.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

TRAF2 associates with cullin neddylation complex assembly.
Title: TRAF2 associates with cullin neddylation complex assembly.
CRISPR-Cas9 screen of E3 ubiquitin ligases identifies TRAF2 and UHRF1 as regulators of HIV latency in primary human T cells.
Title: CRISPR-Cas9 screen of E3 ubiquitin ligases identifies TRAF2 and UHRF1 as regulators of HIV latency in primary human T cells.
Unlocking hepatocellular carcinoma aggression: STAMBPL1-mediated TRAF2 deubiquitination activates WNT/PI3K/NF-kb signaling pathway.
Title: Unlocking hepatocellular carcinoma aggression: STAMBPL1-mediated TRAF2 deubiquitination activates WNT/PI3K/NF-kb signaling pathway.
Silencing of CPNE1-TRAF2 Axis Restrains the Development of Pancreatic Cancer.
Title: Silencing of CPNE1-TRAF2 Axis Restrains the Development of Pancreatic Cancer.
The deubiquitinating enzyme OTUD7b protects dendritic cells from TNF-induced apoptosis by stabilizing the E3 ligase TRAF2.
Title: The deubiquitinating enzyme OTUD7b protects dendritic cells from TNF-induced apoptosis by stabilizing the E3 ligase TRAF2.
TRAF2 promotes M2-polarized tumor-associated macrophage infiltration, angiogenesis and cancer progression by inhibiting autophagy in clear cell renal cell carcinoma.
Title: TRAF2 promotes M2-polarized tumor-associated macrophage infiltration, angiogenesis and cancer progression by inhibiting autophagy in clear cell renal cell carcinoma.
The TRAF2-p62 axis promotes proliferation and survival of liver cancer by activating mTORC1 pathway.
Title: The TRAF2-p62 axis promotes proliferation and survival of liver cancer by activating mTORC1 pathway.
Revisited role of TRAF2 and TRAF2 C-terminal domain in endoplasmic reticulum stress-induced autophagy in HAP1 leukemia cells.
Title: Revisited role of TRAF2 and TRAF2 C-terminal domain in endoplasmic reticulum stress-induced autophagy in HAP1 leukemia cells.
Single nucleotide polymorphisms of TRAF2 and TRAF5 gene in ankylosing spondylitis: a case-control study.
Title: Single nucleotide polymorphisms of TRAF2 and TRAF5 gene in ankylosing spondylitis: a case-control study.
Brief Research Report Regional Difference in TRAF2 and TRAF3 Gene Mutations in Colon Cancers.
Title: Brief Research Report Regional Difference in TRAF2 and TRAF3 Gene Mutations in Colon Cancers.

Submit: New GeneRIF Correction See all GeneRIFs (154)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Nef	nef	The interaction of HIV-1 Nef with TRAF2, TRAF5, and TRAF6 proteins activates NF-kappaB, leading to the degradation of IkappaB-alpha and the increased phosphorylation of IKK-alpha and IKK-beta in monocyte-derived macrophages	PubMed
	nef	HIV-1 Nef interacts with TRAF2, TRAF5, and TRAF6 proteins via its C-terminal region (residues 55-206) in monocyte-derived macrophages	PubMed
	nef	The acidic cluster AQEEEE (residues 64-69) of HIV-1 Nef binds to the residues R393, R403, F447, S454, and F456 of TRAF2	PubMed
	nef	TRAF2 and TRAF6 proteins are required for the HIV-1 Nef-induced tyrosine phosphorylation of STAT1 and STAT2 proteins	PubMed
Vpr	vpr	HIV-1 Vpr-mediated CASP8 (caspase 8) activation is mediated by TRAF-2 in THP-1 cells	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

WI-18599 (e-PCR)
- UniSTS:20015

STS-H09083 (e-PCR)
- UniSTS:75115

RH79117 (e-PCR)
- UniSTS:51861

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables CD40 receptor binding	ISS Inferred from Sequence or Structural Similarity more info
enables enzyme binding	IPI Inferred from Physical Interaction more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables mitogen-activated protein kinase kinase kinase binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein phosphatase binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-containing complex binding	IEA Inferred from Electronic Annotation more info
enables protein-macromolecule adaptor activity	IDA Inferred from Direct Assay more info	PubMed
enables protein-macromolecule adaptor activity	IPI Inferred from Physical Interaction more info	PubMed
enables signaling adaptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables signaling adaptor activity	IEA Inferred from Electronic Annotation more info
enables sphingolipid binding	IDA Inferred from Direct Assay more info	PubMed
enables thioesterase binding	IPI Inferred from Physical Interaction more info	PubMed
enables tumor necrosis factor binding	IPI Inferred from Physical Interaction more info	PubMed
enables tumor necrosis factor receptor binding	IBA Inferred from Biological aspect of Ancestor more info
enables tumor necrosis factor receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables ubiquitin protein ligase activity	IDA Inferred from Direct Assay more info	PubMed
enables ubiquitin protein ligase binding	IDA Inferred from Direct Assay more info	PubMed
enables ubiquitin protein ligase binding	IPI Inferred from Physical Interaction more info	PubMed
enables ubiquitin-protein transferase activity	EXP Inferred from Experiment more info	PubMed
enables ubiquitin-protein transferase activity	IBA Inferred from Biological aspect of Ancestor more info
enables ubiquitin-protein transferase activity	IDA Inferred from Direct Assay more info	PubMed
enables zinc ion binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in CD27 signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in CD40 signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in T cell activation	IDA Inferred from Direct Assay more info	PubMed
involved_in activation of NF-kappaB-inducing kinase activity	IEA Inferred from Electronic Annotation more info
involved_in cellular response to nitric oxide	IEA Inferred from Electronic Annotation more info
acts_upstream_of_positive_effect innate immune response	IDA Inferred from Direct Assay more info	PubMed
involved_in interleukin-17-mediated signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	TAS Traceable Author Statement more info	PubMed
involved_in mRNA stabilization	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of glial cell apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in non-canonical NF-kappaB signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of DNA-binding transcription factor activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of JUN kinase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of NF-kappaB transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of NF-kappaB transcription factor activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of T cell cytokine production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of canonical NF-kappaB signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of extrinsic apoptotic signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of interleukin-2 production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of tumor necrosis factor-mediated signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in programmed necrotic cell death	IEA Inferred from Electronic Annotation more info
involved_in protein K63-linked ubiquitination	IDA Inferred from Direct Assay more info	PubMed
involved_in protein autoubiquitination	IDA Inferred from Direct Assay more info	PubMed
involved_in protein autoubiquitination	TAS Traceable Author Statement more info	PubMed
involved_in protein catabolic process	IEA Inferred from Electronic Annotation more info
involved_in protein-containing complex assembly	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of JNK cascade	IEA Inferred from Electronic Annotation more info
involved_in regulation of apoptotic process	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of immunoglobulin production	IEA Inferred from Electronic Annotation more info
involved_in regulation of protein-containing complex assembly	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to endoplasmic reticulum stress	NAS Non-traceable Author Statement more info	PubMed
involved_in signal transduction	TAS Traceable Author Statement more info	PubMed
involved_in signal transduction involved in regulation of gene expression	IEA Inferred from Electronic Annotation more info
involved_in tumor necrosis factor-mediated signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in tumor necrosis factor-mediated signaling pathway	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
part_of CD40 receptor complex	ISS Inferred from Sequence or Structural Similarity more info
part_of IRE1-TRAF2-ASK1 complex	IDA Inferred from Direct Assay more info	PubMed
part_of TRAF2-GSTP1 complex	IDA Inferred from Direct Assay more info	PubMed
located_in cell cortex	IEA Inferred from Electronic Annotation more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
is_active_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytoplasmic side of plasma membrane	IC Inferred by Curator more info	PubMed
located_in cytoplasmic side of plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info
located_in membrane raft	IEA Inferred from Electronic Annotation more info
located_in nucleoplasm	TAS Traceable Author Statement more info
part_of plasma membrane signaling receptor complex	IBA Inferred from Biological aspect of Ancestor more info
part_of tumor necrosis factor receptor superfamily complex	IDA Inferred from Direct Assay more info	PubMed
part_of ubiquitin ligase complex	IPI Inferred from Physical Interaction more info	PubMed
located_in vesicle membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: TNF receptor-associated factor 2

Names: E3 ubiquitin-protein ligase TRAF2; RING-type E3 ubiquitin transferase TRAF2; tumor necrosis factor type 2 receptor associated protein 3

NP_066961.2

EC 2.3.2.27

XP_011517278.1

EC 2.3.2.27

XP_011517279.1

EC 2.3.2.27

XP_047279784.1

EC 2.3.2.27

XP_047279785.1

EC 2.3.2.27

XP_054219689.1

EC 2.3.2.27

XP_054219690.1

EC 2.3.2.27

XP_054219691.1

EC 2.3.2.27

XP_054219692.1

EC 2.3.2.27

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_021138.4 → NP_066961.2 TNF receptor-associated factor 2

See identical proteins and their annotated locations for NP_066961.2

Status: REVIEWED

Source sequence(s)

BC043492, BC064662

Consensus CDS

CCDS7013.1

UniProtKB/Swiss-Prot

A8K107, B4DPJ7, Q12933, Q7Z337, Q96NT2

UniProtKB/TrEMBL

E5KBQ3

Related

ENSP00000247668.2, ENST00000247668.7

Conserved Domains (5) summary

cd03778
Location:334 → 497

MATH_TRAF2; Tumor Necrosis Factor Receptor (TNFR) Associated Factor (TRAF) family, TRAF2 subfamily, TRAF domain; TRAF molecules serve as adapter proteins that link TNFRs and downstream kinase cascades resulting in the activation of transcription factors and the ...

pfam02176
Location:178 → 235

zf-TRAF; TRAF-type zinc finger

pfam16673
Location:267 → 329

TRAF_BIRC3_bd; TNF receptor-associated factor BIRC3 binding domain

cd16639
Location:32 → 73

RING-HC_TRAF2; RING finger, HC subclass, found in tumor necrosis factor (TNF) receptor-associated factor 2 (TRAF2) and similar proteins

cl28410
Location:28 → 157

RAD18; RING-finger-containing E3 ubiquitin ligase [Signal transduction mechanisms]

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000009.12 Reference GRCh38.p14 Primary Assembly

Range

136881958..136926607

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011518976.4 → XP_011517278.1 TNF receptor-associated factor 2 isoform X2

See identical proteins and their annotated locations for XP_011517278.1

UniProtKB/Swiss-Prot

A8K107, B4DPJ7, Q12933, Q7Z337, Q96NT2

UniProtKB/TrEMBL

E5KBQ3

Conserved Domains (5) summary

cd03778
Location:334 → 497

MATH_TRAF2; Tumor Necrosis Factor Receptor (TNFR) Associated Factor (TRAF) family, TRAF2 subfamily, TRAF domain; TRAF molecules serve as adapter proteins that link TNFRs and downstream kinase cascades resulting in the activation of transcription factors and the ...

pfam02176
Location:178 → 235

zf-TRAF; TRAF-type zinc finger

pfam16673
Location:267 → 329

TRAF_BIRC3_bd; TNF receptor-associated factor BIRC3 binding domain

cd16639
Location:32 → 73

RING-HC_TRAF2; RING finger, HC subclass, found in tumor necrosis factor (TNF) receptor-associated factor 2 (TRAF2) and similar proteins

cl28410
Location:28 → 157

RAD18; RING-finger-containing E3 ubiquitin ligase [Signal transduction mechanisms]
XM_011518977.3 → XP_011517279.1 TNF receptor-associated factor 2 isoform X2

See identical proteins and their annotated locations for XP_011517279.1

UniProtKB/Swiss-Prot

A8K107, B4DPJ7, Q12933, Q7Z337, Q96NT2

UniProtKB/TrEMBL

E5KBQ3

Conserved Domains (5) summary

cd03778
Location:334 → 497

MATH_TRAF2; Tumor Necrosis Factor Receptor (TNFR) Associated Factor (TRAF) family, TRAF2 subfamily, TRAF domain; TRAF molecules serve as adapter proteins that link TNFRs and downstream kinase cascades resulting in the activation of transcription factors and the ...

pfam02176
Location:178 → 235

zf-TRAF; TRAF-type zinc finger

pfam16673
Location:267 → 329

TRAF_BIRC3_bd; TNF receptor-associated factor BIRC3 binding domain

cd16639
Location:32 → 73

RING-HC_TRAF2; RING finger, HC subclass, found in tumor necrosis factor (TNF) receptor-associated factor 2 (TRAF2) and similar proteins

cl28410
Location:28 → 157

RAD18; RING-finger-containing E3 ubiquitin ligase [Signal transduction mechanisms]
XM_047423829.1 → XP_047279785.1 TNF receptor-associated factor 2 isoform X2

UniProtKB/Swiss-Prot

A8K107, B4DPJ7, Q12933, Q7Z337, Q96NT2
XM_047423828.1 → XP_047279784.1 TNF receptor-associated factor 2 isoform X1