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TRAF3 (TNF Receptor Associated Factor 3)

Written2002-08Valérie Kedinger
IGBMC - BP 10142, 67404 ILLKIRCH cedex, France

(Note : for Links provided by Atlas : click)

Identity

Other namesCAP-1
CD40bp
CRAF1
LAP1
HGNC (Hugo) TRAF3
LocusID (NCBI) 7187
Atlas_Id 271
Location 14q32.32  [Link to chromosome band 14q32]
Location_base_pair Starts at 103243816 and ends at 103377837 bp from pter ( according to hg19-Feb_2009)  [Mapping TRAF3.png]
Local_order between a potential gene LOC254285 and the gene encoding for amnionless protein
Fusion genes
(updated 2016)
SLC22A23 (6p25.2) / TRAF3 (14q32.32)TRAF3 (14q32.32) / BMP3 (4q21.21)TRAF3 (14q32.32) / CDC42BPB (14q32.32)
TRAF3 (14q32.32) / MYO16 (13q33.3)TRAF3 (14q32.32) / RCOR1 (14q32.31)UTP14A (Xq26.1) / TRAF3 (14q32.32)

DNA/RNA

Description 13 exons spanning approximately 130 kb
Transcription Three alternatively spliced transcript variants encoding two distinct isoforms have been reported.

Protein

 
Description Isoform 1: 568 amino acids Isoform 2: 543 amino acids
Expression TRAF3 protein is detected in the skin, with a stronger intensity in more differentiated cells in the upper layers of the complex epithelium. TRAF3 is also expressed in the cartilage, in the cardiovascular system, in the trachea, in the salivary gland, in the liver, in the pancreas, in the prostate gland, in the pituitary gland. A gradient of TRAF3 expression appears to exist along the nephron, with progressively higher expression from proximal tubule to collecting duct. In the central nervous system, many but not most neurons in the cerebral cortex, basal ganglia, and brain stem contain at least low levels of TRAF3 protein. In contrast, almost no expression of TRAF3 is detected in the immune system.
Localisation mainly cytoplasmic
Function The TRAF family proteins act at least in part as adapter proteins that recruit other signaling molecules to ligand-bound TNF family receptors. TRAF3 was first described as a molecule that binds the cytoplasmic tail of CD40. Signaling through CD40 in B cells induces rescue from apoptosis, proliferation, differentiation, Ig production, class switching and expression of co-stimulatory molecules. Insights into the in vivo functions of TRAF3 have come from generation of mice deficient for TRAF3. These mice are depleted in all lineages of peripheral leucocytes, and die shortly after birth. However, B cells from TRAF3-/- upregulate CD23 and proliferate normally in response to CD40 ligand stimulation. Moreover, fetal liver cells from TRAF3 deficient mice can reconstitute the immune system of irradiated wild type mice, although isotype switching in response to T-dependent antigens is defective. Thus, TRAF3 is not required for CD40 signaling, but appears important in T cell-dependent immune responses. These effects of TRAF3 may be mediated through other TNF receptor family members : TRAF3 can bind directly to the cytosolic domains of CD27, CD30, LTbR, LMP-1, and also binds indirectly TNF-R2.
Homology TRAF3 belongs to a family of six proteins (TRAF1 to 6), sharing a common structural organization. TRAF3 counterparts are found in mouse, fly and worm.

Implicated in

Note
Disease Hodgkin disease, Lymphomas.
  

Bibliography

Hodgkin disease: pharmacologic intervention of the CD40-NF kappa B pathway by a protease inhibitor.
Annunziata CM, Safiran YJ, Irving SG, Kasid UN, Cossman J
Blood. 2000 ; 96 (8) : 2841-2848.
PMID 11023520
 
Tumor necrosis factor receptor-associated factors (TRAFs).
Bradley JR, Pober JS
Oncogene. 2001 ; 20 (44) : 6482-6491.
PMID 11607847
 
Involvement of CRAF1, a relative of TRAF, in CD40 signaling.
Cheng G, Cleary AM, Ye ZS, Hong DI, Lederman S, Baltimore D
Science (New York, N.Y.). 1995 ; 267 (5203) : 1494-1498.
PMID 7533327
 
Membrane localization of TRAF 3 enables JNK activation.
Dadgostar H, Cheng G
The Journal of biological chemistry. 2000 ; 275 (4) : 2539-2544.
PMID 10644711
 
Immunohistochemical analysis of in vivo patterns of TRAF-3 expression, a member of the TNF receptor-associated factor family.
Krajewski S, Zapata JM, Krajewska M, VanArsdale T, Shabaik A, Gascoyne RD, Reed JC
Journal of immunology (Baltimore, Md. : 1950). 1997 ; 159 (12) : 5841-5852.
PMID 9550380
 
Epstein-Barr virus and a cellular signaling pathway in lymphomas from immunosuppressed patients.
Liebowitz D
The New England journal of medicine. 1998 ; 338 (20) : 1413-1421.
PMID 9580648
 
Targeted disruption of TRAF3 leads to postnatal lethality and defective T-dependent immune responses.
Xu Y, Cheng G, Baltimore D
Immunity. 1996 ; 5 (5) : 407-415.
PMID 8934568
 
A single gene for human TRAF-3 at chromosome 14q32.3 encodes a variety of mRNA species by alternative polyadenylation, mRNA splicing and transcription initiation.
van Eyndhoven WG, Frank D, Kalachikov S, Cleary AM, Hong DI, Cho E, Nasr S, Perez AJ, Mackus WJ, Cayanis E, Wellington S, Fischer SG, Warburton D, Lederman S
Molecular immunology. 1998 ; 35 (18) : 1189-1206.
PMID 10199393
 

Citation

This paper should be referenced as such :
Kedinger, V
TRAF3 (TNF Receptor Associated Factor 3)
Atlas Genet Cytogenet Oncol Haematol. 2003;7(1):4-5.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/TRAF3ID271.html


External links

Nomenclature
HGNC (Hugo)TRAF3   12033
Cards
AtlasTRAF3ID271
Entrez_Gene (NCBI)TRAF3  7187  TNF receptor associated factor 3
AliasesCAP-1; CAP1; CD40bp; CRAF1; 
IIAE5; LAP1
GeneCards (Weizmann)TRAF3
Ensembl hg19 (Hinxton)ENSG00000131323 [Gene_View]  chr14:103243816-103377837 [Contig_View]  TRAF3 [Vega]
Ensembl hg38 (Hinxton)ENSG00000131323 [Gene_View]  chr14:103243816-103377837 [Contig_View]  TRAF3 [Vega]
ICGC DataPortalENSG00000131323
TCGA cBioPortalTRAF3
AceView (NCBI)TRAF3
Genatlas (Paris)TRAF3
WikiGenes7187
SOURCE (Princeton)TRAF3
Genomic and cartography
GoldenPath hg19 (UCSC)TRAF3  -     chr14:103243816-103377837 +  14q32.32   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)TRAF3  -     14q32.32   [Description]    (hg38-Dec_2013)
EnsemblTRAF3 - 14q32.32 [CytoView hg19]  TRAF3 - 14q32.32 [CytoView hg38]
Mapping of homologs : NCBITRAF3 [Mapview hg19]  TRAF3 [Mapview hg38]
OMIM601896   614849   
Gene and transcription
Genbank (Entrez)AF110908 AK303172 BC075086 BC075087 BQ000015
RefSeq transcript (Entrez)NM_001199427 NM_003300 NM_145725 NM_145726
RefSeq genomic (Entrez)NC_000014 NC_018925 NG_027973 NT_026437 NW_004929393
Consensus coding sequences : CCDS (NCBI)TRAF3
Cluster EST : UnigeneHs.510528 [ NCBI ]
CGAP (NCI)Hs.510528
Alternative Splicing GalleryENSG00000131323
Gene ExpressionTRAF3 [ NCBI-GEO ]   TRAF3 [ EBI - ARRAY_EXPRESS ]   TRAF3 [ SEEK ]   TRAF3 [ MEM ]
Gene Expression Viewer (FireBrowse)TRAF3 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)7187
GTEX Portal (Tissue expression)TRAF3
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ13114 (Uniprot)
NextProtQ13114  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ13114
Splice isoforms : SwissVarQ13114 (Swissvar)
Catalytic activity : Enzyme6.3.2.- [ Enzyme-Expasy ]   6.3.2.-6.3.2.- [ IntEnz-EBI ]   6.3.2.- [ BRENDA ]   6.3.2.- [ KEGG ]   
PhosPhoSitePlusQ13114
Domaine pattern : Prosite (Expaxy)MATH (PS50144)    ZF_RING_1 (PS00518)    ZF_RING_2 (PS50089)    ZF_TRAF (PS50145)   
Domains : Interpro (EBI)MATH/TRAF_dom    SIAH-type    TNF_rcpt--assoc_TRAF    TRAF-like    TRAF3    Znf_RING    Znf_RING/FYVE/PHD    Znf_RING_CS    Znf_TRAF   
Domain families : Pfam (Sanger)zf-TRAF (PF02176)   
Domain families : Pfam (NCBI)pfam02176   
Domain families : Smart (EMBL)MATH (SM00061)  RING (SM00184)  
DMDM Disease mutations7187
Blocks (Seattle)TRAF3
PDB (SRS)1FLK    1FLL    1KZZ    1L0A    1RF3    1ZMS    2ECY    2GKW   
PDB (PDBSum)1FLK    1FLL    1KZZ    1L0A    1RF3    1ZMS    2ECY    2GKW   
PDB (IMB)1FLK    1FLL    1KZZ    1L0A    1RF3    1ZMS    2ECY    2GKW   
PDB (RSDB)1FLK    1FLL    1KZZ    1L0A    1RF3    1ZMS    2ECY    2GKW   
Structural Biology KnowledgeBase1FLK    1FLL    1KZZ    1L0A    1RF3    1ZMS    2ECY    2GKW   
SCOP (Structural Classification of Proteins)1FLK    1FLL    1KZZ    1L0A    1RF3    1ZMS    2ECY    2GKW   
CATH (Classification of proteins structures)1FLK    1FLL    1KZZ    1L0A    1RF3    1ZMS    2ECY    2GKW   
SuperfamilyQ13114
Human Protein AtlasENSG00000131323
Peptide AtlasQ13114
HPRD03539
IPIIPI00297473   IPI00973170   IPI00744216   
Protein Interaction databases
DIP (DOE-UCLA)Q13114
IntAct (EBI)Q13114
FunCoupENSG00000131323
BioGRIDTRAF3
STRING (EMBL)TRAF3
ZODIACTRAF3
Ontologies - Pathways
QuickGOQ13114
Ontology : AmiGOregulation of cytokine production  toll-like receptor signaling pathway  ubiquitin-protein transferase activity  signal transducer activity  tumor necrosis factor receptor binding  protein binding  mitochondrion  endosome  cytosol  apoptotic process  signal transduction  Toll signaling pathway  zinc ion binding  cytoplasmic side of plasma membrane  protein ubiquitination  ligase activity  protein kinase binding  protein phosphatase binding  regulation of proteolysis  ubiquitin protein ligase binding  thioesterase binding  negative regulation of NF-kappaB transcription factor activity  negative regulation of type I interferon production  regulation of interferon-beta production  tumor necrosis factor-mediated signaling pathway  tumor necrosis factor-mediated signaling pathway  CD40 receptor complex  TRIF-dependent toll-like receptor signaling pathway  regulation of apoptotic process  innate immune response  regulation of defense response to virus  
Ontology : EGO-EBIregulation of cytokine production  toll-like receptor signaling pathway  ubiquitin-protein transferase activity  signal transducer activity  tumor necrosis factor receptor binding  protein binding  mitochondrion  endosome  cytosol  apoptotic process  signal transduction  Toll signaling pathway  zinc ion binding  cytoplasmic side of plasma membrane  protein ubiquitination  ligase activity  protein kinase binding  protein phosphatase binding  regulation of proteolysis  ubiquitin protein ligase binding  thioesterase binding  negative regulation of NF-kappaB transcription factor activity  negative regulation of type I interferon production  regulation of interferon-beta production  tumor necrosis factor-mediated signaling pathway  tumor necrosis factor-mediated signaling pathway  CD40 receptor complex  TRIF-dependent toll-like receptor signaling pathway  regulation of apoptotic process  innate immune response  regulation of defense response to virus  
Pathways : BIOCARTACD40L Signaling Pathway [Genes]    TACI and BCMA stimulation of B cell immune responses. [Genes]    TNFR2 Signaling Pathway [Genes]   
Pathways : KEGGNF-kappa B signaling pathway    Toll-like receptor signaling pathway    RIG-I-like receptor signaling pathway    TNF signaling pathway    Hepatitis C    Herpes simplex infection    Epstein-Barr virus infection    Pathways in cancer    Viral carcinogenesis    Small cell lung cancer   
REACTOMEQ13114 [protein]
REACTOME PathwaysR-HSA-918233 TRAF3-dependent IRF activation pathway [pathway]
REACTOME PathwaysR-HSA-936440 Negative regulators of RIG-I/MDA5 signaling [pathway]
REACTOME PathwaysR-HSA-5668541 TNFR2 non-canonical NF-kB pathway [pathway]
REACTOME PathwaysR-HSA-5602571 TRAF3 deficiency - HSE [pathway]
REACTOME PathwaysR-HSA-5676594 TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway [pathway]
REACTOME PathwaysR-HSA-936964 Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon [pathway]
NDEx NetworkTRAF3
Atlas of Cancer Signalling NetworkTRAF3
Wikipedia pathwaysTRAF3
Orthology - Evolution
OrthoDB7187
GeneTree (enSembl)ENSG00000131323
Phylogenetic Trees/Animal Genes : TreeFamTRAF3
Homologs : HomoloGeneTRAF3
Homology/Alignments : Family Browser (UCSC)TRAF3
Gene fusions - Rearrangements
Fusion : MitelmanSLC22A23/TRAF3 [6p25.2/14q32.32]  [t(6;14)(p25;q32)]  
Fusion : MitelmanTRAF3/BMP3 [14q32.32/4q21.21]  [t(4;14)(q21;q32)]  
Fusion : MitelmanTRAF3/CDC42BPB [14q32.32/14q32.32]  [t(14;14)(q32;q32)]  
Fusion : MitelmanTRAF3/MYO16 [14q32.32/13q33.3]  [t(13;14)(q33;q32)]  
Fusion : MitelmanTRAF3/RCOR1 [14q32.32/14q32.31]  [t(14;14)(q32;q32)]  
Fusion: TCGASLC22A23 6p25.2 TRAF3 14q32.32 LUSC
Fusion: TCGATRAF3 14q32.32 BMP3 4q21.21 LUSC
Fusion: TCGATRAF3 14q32.32 CDC42BPB 14q32.32 HNSC
Fusion: TCGATRAF3 14q32.32 MYO16 13q33.3 BRCA
Fusion: TCGATRAF3 14q32.32 RCOR1 14q32.31 BRCA
Polymorphisms : SNP, variants
NCBI Variation ViewerTRAF3 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)TRAF3
dbVarTRAF3
ClinVarTRAF3
1000_GenomesTRAF3 
Exome Variant ServerTRAF3
ExAC (Exome Aggregation Consortium)TRAF3 (select the gene name)
Genetic variants : HAPMAP7187
Genomic Variants (DGV)TRAF3 [DGVbeta]
Mutations
ICGC Data PortalTRAF3 
TCGA Data PortalTRAF3 
Broad Tumor PortalTRAF3
OASIS PortalTRAF3 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICTRAF3 
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
LOVD (Leiden Open Variation Database)**PUBLIC** CCHMC Molecular Genetics Laboratory Mutation Database
BioMutasearch TRAF3
DgiDB (Drug Gene Interaction Database)TRAF3
DoCM (Curated mutations)TRAF3 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)TRAF3 (select a term)
intoGenTRAF3
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
Diseases
DECIPHER (Syndromes)14:103243816-103377837  ENSG00000131323
CONAN: Copy Number AnalysisTRAF3 
Mutations and Diseases : HGMDTRAF3
OMIM601896    614849   
MedgenTRAF3
Genetic Testing Registry TRAF3
NextProtQ13114 [Medical]
TSGene7187
GENETestsTRAF3
Huge Navigator TRAF3 [HugePedia]
snp3D : Map Gene to Disease7187
BioCentury BCIQTRAF3
ClinGenTRAF3
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD7187
Chemical/Pharm GKB GenePA36710
Clinical trialTRAF3
Miscellaneous
canSAR (ICR)TRAF3 (select the gene name)
Other databasehttp://cancergenome.broadinstitute.org/index.php?tgene=TRAF3
Probes
Litterature
PubMed192 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineTRAF3
EVEXTRAF3
GoPubMedTRAF3
iHOPTRAF3
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Wed Sep 28 15:53:46 CEST 2016

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