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Q13114 (TRAF3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 164. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
TNF receptor-associated factor 3

EC=6.3.2.-
Alternative name(s):
CAP-1
CD40 receptor-associated factor 1
Short name=CRAF1
CD40-binding protein
Short name=CD40BP
LMP1-associated protein 1
Short name=LAP1
Gene names
Name:TRAF3
Synonyms:CAP1, CRAF1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length568 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.27 Ref.28 Ref.29 Ref.33 Ref.34 Ref.35

Subunit structure

Homotrimer. Heterotrimer with TRAF2 and TRAF5. Interacts with LTBR/TNFRSF3, TNFRSF4, TNFRSF5/CD40, TNFRSF8/CD30, TNFRSF13C TNFRSF17/BCMA, TLR4 and EDAR. Interacts with MAP3K5, MAP3K14, TRAIP/TRIP, TDP2/TTRAP, TANK/ITRAF and TRAF3IP1. Interaction with TNFRSF5/CD40 is modulated by TANK/ITRAF, which competes for the same binding site. Interacts with TICAM1. Interacts with TRAFD1. Interacts with OTUB1, OTUB2 and OTUD5. Interacts with RNF216, MAVS, OPTN and TBK1. Identified in a complex with TRAF2, MAP3K14 and BIRC3. Interacts with BIRC2 and BIRC3. Upon exposure to bacterial lipopolysaccharide (LPS), recruited to a transient complex containing TLR4, TRAF3, TRAF6, IKBKG, MAP3K7, MYD88, TICAM1, BIRC2, BIRC3 and UBE2N By similarity. Interacts with Epstein-Barr virus protein LMP1. Interacts (via RING-type zinc finger domain) with SRC. Interacts with CARD14. Ref.1 Ref.2 Ref.3 Ref.4 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28 Ref.29 Ref.30 Ref.31 Ref.32 Ref.33 Ref.36 Ref.37 Ref.40 Ref.41 Ref.42

Subcellular location

Cytoplasm Probable. Endosome By similarity. Mitochondrion. Note: Undergoes endocytosis together with TLR4 upon LPS signaling By similarity. Associated with mitochondria in response to virus. Ref.27 Ref.33

Domain

The MATH/TRAF domain binds to receptor cytoplasmic domains.

The Ring-type zinc finger domain is required for its function in down-regulation of NFKB2 proteolytic processing By similarity.

Post-translational modification

Undergoes 'Lys-48'-linked polyubiquitination, leading to its proteasomal degradation in response to signaling by TNFSF13B, TLR4 or through CD40. 'Lys-48'-linked polyubiquitinated form is deubiquitinated by OTUD7B, preventing TRAF3 proteolysis and over-activation of non-canonical NF-kappa-B. Undergoes 'Lys-63'-linked ubiquitination during early stages of virus infection, and 'Lys-48'-linked ubiquitination during later stages. Undergoes both 'Lys-48'-linked and 'Lys-63'-linked ubiquitination in response to TLR3 and TLR4 signaling. Deubiquitinated by OTUB1, OTUB2 and OTUD5.

Involvement in disease

Herpes simplex encephalitis 3 (HSE3) [MIM:614849]: A rare complication of human herpesvirus 1 (HHV-1) infection, occurring in only a small minority of HHV-1 infected individuals. HSE is characterized by hemorrhagic necrosis of parts of the temporal and frontal lobes. Onset is over several days and involves fever, headache, seizures, stupor, and often coma, frequently with a fatal outcome.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.44

Sequence similarities

Belongs to the TNF receptor-associated factor family. A subfamily.

Contains 1 MATH domain.

Contains 1 RING-type zinc finger.

Contains 2 TRAF-type zinc fingers.

Ontologies

Keywords
   Biological processApoptosis
Immunity
Ubl conjugation pathway
   Cellular componentCytoplasm
Endosome
Mitochondrion
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
   DomainCoiled coil
Repeat
Zinc-finger
   LigandMetal-binding
Zinc
   Molecular functionLigase
   PTMIsopeptide bond
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processMyD88-independent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

TRIF-dependent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

Toll signaling pathway

Inferred from electronic annotation. Source: InterPro

apoptotic process

Traceable author statement PubMed 10799510. Source: ProtInc

innate immune response

Traceable author statement. Source: Reactome

negative regulation of NF-kappaB transcription factor activity

Inferred from mutant phenotype Ref.34. Source: UniProtKB

negative regulation of type I interferon production

Traceable author statement. Source: Reactome

regulation of apoptotic process

Inferred from electronic annotation. Source: InterPro

regulation of cytokine production

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of defense response to virus

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of interferon-beta production

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of proteolysis

Inferred from mutant phenotype Ref.34. Source: UniProtKB

signal transduction

Traceable author statement Ref.3. Source: ProtInc

toll-like receptor 3 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 4 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

tumor necrosis factor-mediated signaling pathway

Inferred from mutant phenotype Ref.34. Source: UniProtKB

   Cellular_componentCD40 receptor complex

Inferred from sequence or structural similarity. Source: BHF-UCL

cytoplasmic side of plasma membrane

Inferred from sequence or structural similarity. Source: BHF-UCL

cytosol

Traceable author statement. Source: Reactome

endosome

Inferred from electronic annotation. Source: UniProtKB-SubCell

mitochondrion

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionsignal transducer activity

Traceable author statement Ref.3Ref.4. Source: ProtInc

thioesterase binding

Inferred from physical interaction PubMed 11279055. Source: UniProtKB

ubiquitin protein ligase binding

Inferred from physical interaction PubMed 11279055. Source: UniProtKB

ubiquitin-protein ligase activity

Inferred from electronic annotation. Source: InterPro

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q13114-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q13114-2)

The sequence of this isoform differs from the canonical sequence as follows:
     191-273: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 568568TNF receptor-associated factor 3
PRO_0000056401

Regions

Domain415 – 560146MATH
Zinc finger68 – 7710RING-type
Zinc finger135 – 19056TRAF-type 1
Zinc finger191 – 24959TRAF-type 2
Coiled coil267 – 33872 Potential

Amino acid modifications

Cross-link107Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Cross-link156Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Natural variations

Alternative sequence191 – 27383Missing in isoform 2.
VSP_040040
Natural variant1181R → W in HSE3. Ref.44
VAR_069081
Natural variant1291M → T. Ref.3 Ref.4
Corresponds to variant rs1131877 [ dbSNP | Ensembl ].
VAR_052149

Experimental info

Mutagenesis4411Y → A: Abolishes interaction with RNF216; when associated with A-443. Ref.31
Mutagenesis4431Q → A: Abolishes interaction with RNF216; when associated with A-441. Ref.31
Mutagenesis4591Y → A: Abolishes interaction with LTBR, CD40 and TANK. Ref.40
Mutagenesis5121F → E: Abolishes interaction with LTBR, CD40 and TANK. Ref.40
Mutagenesis5211F → A: Abolishes interaction with LTBR, CD40 and TANK. Ref.40
Sequence conflict1341Missing in AAA56753. Ref.4
Sequence conflict1581L → F in BAH13910. Ref.6
Sequence conflict218 – 24225Missing in AAA68195. Ref.3
Sequence conflict3391P → S in AAA68195. Ref.3
Sequence conflict4051R → G in AAA56753. Ref.4

Secondary structure

................................................... 568
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 17, 2006. Version 2.
Checksum: 9456E440C0A90FBF

FASTA56864,490
        10         20         30         40         50         60 
MESSKKMDSP GALQTNPPLK LHTDRSAGTP VFVPEQGGYK EKFVKTVEDK YKCEKCHLVL 

        70         80         90        100        110        120 
CSPKQTECGH RFCESCMAAL LSSSSPKCTA CQESIVKDKV FKDNCCKREI LALQIYCRNE 

       130        140        150        160        170        180 
SRGCAEQLML GHLLVHLKND CHFEELPCVR PDCKEKVLRK DLRDHVEKAC KYREATCSHC 

       190        200        210        220        230        240 
KSQVPMIALQ KHEDTDCPCV VVSCPHKCSV QTLLRSELSA HLSECVNAPS TCSFKRYGCV 

       250        260        270        280        290        300 
FQGTNQQIKA HEASSAVQHV NLLKEWSNSL EKKVSLLQNE SVEKNKSIQS LHNQICSFEI 

       310        320        330        340        350        360 
EIERQKEMLR NNESKILHLQ RVIDSQAEKL KELDKEIRPF RQNWEEADSM KSSVESLQNR 

       370        380        390        400        410        420 
VTELESVDKS AGQVARNTGL LESQLSRHDQ MLSVHDIRLA DMDLRFQVLE TASYNGVLIW 

       430        440        450        460        470        480 
KIRDYKRRKQ EAVMGKTLSL YSQPFYTGYF GYKMCARVYL NGDGMGKGTH LSLFFVIMRG 

       490        500        510        520        530        540 
EYDALLPWPF KQKVTLMLMD QGSSRRHLGD AFKPDPNSSS FKKPTGEMNI ASGCPVFVAQ 

       550        560 
TVLENGTYIK DDTIFIKVIV DTSDLPDP 

« Hide

Isoform 2 [UniParc].

Checksum: 1280A3E1B054768D
Show »

FASTA48555,306

References

« Hide 'large scale' references
[1]"A novel RING finger protein interacts with the cytoplasmic domain of CD40."
Hu H.M., O'Rourke K., Boguski M.S., Dixit V.M.
J. Biol. Chem. 269:30069-30072(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH TNFRSF5.
[2]"The Epstein-Barr virus transforming protein LMP1 engages signaling proteins for the tumor necrosis factor receptor family."
Mosialos G., Birkenbach M., Yalamanchili R., VanArsdale T., Ware C., Kieff E.
Cell 80:389-399(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHARACTERIZATION, INTERACTION WITH EBV LMP-1.
Tissue: Lymphoma.
[3]"A novel member of the TRAF family of putative signal transducing proteins binds to the cytosolic domain of CD40."
Sato T., Irie S., Reed J.C.
FEBS Lett. 358:113-118(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH TNFRSF5, VARIANT THR-129.
Tissue: Fetal brain.
[4]"Involvement of CRAF1, a relative of TRAF, in CD40 signaling."
Cheng G., Cleary A.M., Ye Z.S., Hong D.I., Lederman S., Baltimore D.
Science 267:1494-1498(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH TNFRSF5, VARIANT THR-129.
[5]"Full-length cDNA libraries and normalization."
Li W.B., Gruber C., Jessee J., Polayes D.
Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Fetal brain.
[6]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Thymus.
[7]"The DNA sequence and analysis of human chromosome 14."
Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H. expand/collapse author list , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J.
Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[9]"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 W.G., Frank D., Kalachikov S., Cleary A.M., Hong D.I., Cho E., Nasr S., Perez A.J., Mackus W.J.M., Cayanis E., Wellington S., Fischer S.G., Warburton D., Lederman S.
Mol. Immunol. 35:1189-1206(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 536-568.
[10]"TRAF5, an activator of NF-kappaB and putative signal transducer for the lymphotoxin-beta receptor."
Nakano H., Oshima H., Chung W., Williams-Abbott L., Ware C.F., Yagita H., Okumura K.
J. Biol. Chem. 271:14661-14664(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH LTBR.
[11]"I-TRAF is a novel TRAF-interacting protein that regulates TRAF-mediated signal transduction."
Rothe M., Xiong J., Shu H.-B., Williamson K., Goddard A., Goeddel D.V.
Proc. Natl. Acad. Sci. U.S.A. 93:8241-8246(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TANK.
[12]"Binding sites of cytoplasmic effectors TRAF1, 2, and 3 on CD30 and other members of the TNF receptor superfamily."
Boucher L.-M., Marengere L.E., Lu Y., Thukral S., Mak T.W.
Biochem. Biophys. Res. Commun. 233:592-600(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TNFRSF8.
[13]"Herpesvirus entry mediator, a member of the tumor necrosis factor receptor (TNFR) family, interacts with members of the TNFR-associated factor family and activates the transcription factors NF-kappaB and AP-1."
Marsters S.A., Ayres T.M., Skubatch M., Gray C.L., Rothe M., Ashkenazi A.
J. Biol. Chem. 272:14029-14032(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TNFRSF14.
[14]"Tumor necrosis factor (TNF)-mediated kinase cascades: bifurcation of nuclear factor-kappaB and c-jun N-terminal kinase (JNK/SAPK) pathways at TNF receptor-associated factor 2."
Song H.Y., Regnier C.H., Kirschning C.J., Goeddel D.V., Rothe M.
Proc. Natl. Acad. Sci. U.S.A. 94:9792-9796(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MAP3K14.
[15]"CD40-tumor necrosis factor receptor-associated factor (TRAF) interactions: regulation of CD40 signaling through multiple TRAF binding sites and TRAF hetero-oligomerization."
Pullen S.S., Miller H.G., Everdeen D.S., Dang T.T., Crute J.J., Kehry M.R.
Biochemistry 37:11836-11845(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TNFRSF5 AND TRAF5.
[16]"Activation of OX40 signal transduction pathways leads to tumor necrosis factor receptor-associated factor (TRAF) 2- and TRAF5-mediated NF-kappaB activation."
Kawamata S., Hori T., Imura A., Takaori-Kondo A., Uchiyama T.
J. Biol. Chem. 273:5808-5814(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TNFRSF4.
[17]"The TRAF family of signal transducers mediates NF-kappaB activation by the TRANCE receptor."
Wong B.R., Josien R., Lee S.Y., Vologodskaia M., Steinman R.M., Choi Y.
J. Biol. Chem. 273:28355-28359(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TNFRSF11A.
[18]"ASK1 is essential for JNK/SAPK activation by TRAF2."
Nishitoh H., Saitoh M., Mochida Y., Takeda K., Nakano H., Rothe M., Miyazono K., Ichijo H.
Mol. Cell 2:389-395(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MAP3K5.
[19]"4-1BB and Ox40 are members of a tumor necrosis factor (TNF)-nerve growth factor receptor subfamily that bind TNF receptor-associated factors and activate nuclear factor kappaB."
Arch R.H., Thompson C.B.
Mol. Cell. Biol. 18:558-565(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TNFRSF4 AND TNFRSF9.
[20]"Identification of a novel activation-inducible protein of the tumor necrosis factor receptor superfamily and its ligand."
Kwon B., Yu K.-Y., Ni J., Yu G.-L., Jang I.-K., Kim Y.-J., Xing L., Liu D., Wang S.-X., Kwon B.S.
J. Biol. Chem. 274:6056-6061(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TNFRSF18.
Tissue: T-cell.
[21]"Mediation of TNF receptor-associated factor effector functions by apoptosis signal-regulating kinase-1 (ASK1)."
Hoeflich K.P., Yeh W.C., Yao Z., Mak T.W., Woodgett J.R.
Oncogene 18:5814-5820(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MAP3K5.
[22]"TAJ, a novel member of the tumor necrosis factor receptor family, activates the c-Jun N-terminal kinase pathway and mediates caspase-independent cell death."
Eby M.T., Jasmin A., Kumar A., Sharma K., Chaudhary P.M.
J. Biol. Chem. 275:15336-15342(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TNFRSF19.
[23]"TTRAP, a novel protein that associates with CD40, tumor necrosis factor (TNF) receptor-75 and TNF receptor-associated factors (TRAFs), and that inhibits nuclear factor-kappa B activation."
Pype S., Declercq W., Ibrahimi A., Michiels C., Van Rietschoten J.G.I., Dewulf N., de Boer M., Vandenabeele P., Huylebroeck D., Remacle J.E.
J. Biol. Chem. 275:18586-18593(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TTRAP.
[24]"MIP-T3, a novel protein linking tumor necrosis factor receptor-associated factor 3 to the microtubule network."
Ling L., Goeddel D.V.
J. Biol. Chem. 275:23852-23860(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TRAF3IP1.
[25]"TNF receptor family member BCMA (B cell maturation) associates with TNF receptor-associated factor (TRAF) 1, TRAF2, and TRAF3 and activates NF-kappa B, elk-1, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase."
Hatzoglou A., Roussel J., Bourgeade M.-F., Rogier E., Madry C., Inoue J., Devergne O., Tsapis A.
J. Immunol. 165:1322-1330(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TNFRSF17.
[26]"The ectodermal dysplasia receptor activates the nuclear factor-kappaB, JNK, and cell death pathways and binds to ectodysplasin A."
Kumar A., Eby M.T., Sinha S., Jasmin A., Chaudhary P.M.
J. Biol. Chem. 276:2668-2677(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH EDAR.
[27]"TRAF3 forms heterotrimers with TRAF2 and modulates its ability to mediate NF-{kappa}B activation."
He L., Grammer A.C., Wu X., Lipsky P.E.
J. Biol. Chem. 279:55855-55865(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, SUBUNIT.
[28]"Regulation of the NF-kappaB-inducing kinase by tumor necrosis factor receptor-associated factor 3-induced degradation."
Liao G., Zhang M., Harhaj E.W., Sun S.C.
J. Biol. Chem. 279:26243-26250(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PROTEASOMAL DEGRADATION, INTERACTION WITH MAP3K14.
[29]"DUBA: a deubiquitinase that regulates type I interferon production."
Kayagaki N., Phung Q., Chan S., Chaudhari R., Quan C., O'Rourke K.M., Eby M., Pietras E., Cheng G., Bazan J.F., Zhang Z., Arnott D., Dixit V.M.
Science 318:1628-1632(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH OTUD5 AND TBK1, FUNCTION AS E3 PROTEIN-UBIQUITIN LIGASE, UBIQUITINATION.
[30]"The tyrosine kinase c-Src enhances RIG-I (retinoic acid-inducible gene I)-elicited antiviral signaling."
Johnsen I.B., Nguyen T.T., Bergstroem B., Fitzgerald K.A., Anthonsen M.W.
J. Biol. Chem. 284:19122-19131(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SRC.
[31]"The E3 ubiquitin ligase Triad3A negatively regulates the RIG-I/MAVS signaling pathway by targeting TRAF3 for degradation."
Nakhaei P., Mesplede T., Solis M., Sun Q., Zhao T., Yang L., Chuang T.H., Ware C.F., Lin R., Hiscott J.
PLoS Pathog. 5:E1000650-E1000650(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION, MUTAGENESIS OF TYR-441 AND GLN-443, INTERACTION WITH RNF216 AND MAVS.
[32]"Regulation of virus-triggered signaling by OTUB1- and OTUB2-mediated deubiquitination of TRAF3 and TRAF6."
Li S., Zheng H., Mao A.P., Zhong B., Li Y., Liu Y., Gao Y., Ran Y., Tien P., Shu H.B.
J. Biol. Chem. 285:4291-4297(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION, INTERACTION WITH OTUB1 AND OTUB2.
[33]"Virus-triggered ubiquitination of TRAF3/6 by cIAP1/2 is essential for induction of interferon-beta (IFN-beta) and cellular antiviral response."
Mao A.P., Li S., Zhong B., Li Y., Yan J., Li Q., Teng C., Shu H.B.
J. Biol. Chem. 285:9470-9476(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH BIRC2 AND BIRC3, SUBCELLULAR LOCATION, UBIQUITINATION.
[34]"TRAF3 controls activation of the canonical and alternative NFkappaB by the lymphotoxin beta receptor."
Bista P., Zeng W., Ryan S., Bailly V., Browning J.L., Lukashev M.E.
J. Biol. Chem. 285:12971-12978(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[35]"Ubiquitin ligase Smurf1 targets TRAF family proteins for ubiquitination and degradation."
Li S., Lu K., Wang J., An L., Yang G., Chen H., Cui Y., Yin X., Xie P., Xing G., He F., Zhang L.
Mol. Cell. Biochem. 338:11-17(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION, FUNCTION.
[36]"Optineurin negatively regulates the induction of IFNbeta in response to RNA virus infection."
Mankouri J., Fragkoudis R., Richards K.H., Wetherill L.F., Harris M., Kohl A., Elliott R.M., Macdonald A.
PLoS Pathog. 6:E1000778-E1000778(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH OPTN AND TBK1.
[37]"Alternative splicing of CARMA2/CARD14 transcripts generates protein variants with differential effect on NF-kappaB activation and endoplasmic reticulum stress-induced cell death."
Scudiero I., Zotti T., Ferravante A., Vessichelli M., Vito P., Stilo R.
J. Cell. Physiol. 226:3121-3131(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CARD14.
[38]"Molecular basis for CD40 signaling mediated by TRAF3."
Ni C.Z., Welsh K., Leo E., Chiou C.K., Wu H., Reed J.C., Ely K.R.
Proc. Natl. Acad. Sci. U.S.A. 97:10395-10399(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 341-568, X-RAY CRYSTALLOGRAPHY (3.5 ANGSTROMS) OF 341-568 IN COMPLEX WITH TNFRSF5.
[39]"Downstream regulator TANK binds to the CD40 recognition site on TRAF3."
Li C., Ni C.Z., Havert M.L., Cabezas E., He J., Kaiser D., Reed J.C., Satterthwait A.C., Cheng G., Ely K.R.
Structure 10:403-411(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.5 ANGSTROMS) OF 377-568 IN COMPLEX WITH TANK, X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 377-568 IN COMPLEX WITH TNFRSF5.
[40]"Structurally distinct recognition motifs in lymphotoxin-beta receptor and CD40 for tumor necrosis factor receptor-associated factor (TRAF)-mediated signaling."
Li C., Norris P.S., Ni C.Z., Havert M.L., Chiong E.M., Tran B.R., Cabezas E., Reed J.C., Satterthwait A.C., Ware C.F., Ely K.R.
J. Biol. Chem. 278:50523-50529(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.5 ANGSTROMS) OF 377-568 IN COMPLEX WITH LTBR, MUTAGENESIS OF TYR-459; PHE-512 AND PHE-521, INTERACTION WITH TANK AND CD40, SUBUNIT.
[41]"Key molecular contacts promote recognition of the BAFF receptor by TNF receptor-associated factor 3: implications for intracellular signaling regulation."
Ni C.Z., Oganesyan G., Welsh K., Zhu X., Reed J.C., Satterthwait A.C., Cheng G., Ely K.R.
J. Immunol. 173:7394-7400(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 377-568 IN COMPLEX WITH TNFRSF13C PEPTIDE, SUBUNIT, INTERACTION WITH TNFRSF13C.
[42]"LMP1 protein from the Epstein-Barr virus is a structural CD40 decoy in B lymphocytes for binding to TRAF3."
Wu S., Xie P., Welsh K., Li C., Ni C.Z., Zhu X., Reed J.C., Satterthwait A.C., Bishop G.A., Ely K.R.
J. Biol. Chem. 280:33620-33626(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 377-568 IN COMPLEX WITH EPSTEIN-BARR VIRUS PROTEIN LMP1, SUBUNIT.
[43]"Solution structure of the zinc finger, C3HC4 type (RING finger) domain of TNF receptor-associated factor 3."
RIKEN structural genomics initiative (RSGI)
Submitted (FEB-2008) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 43-101.
[44]"Human TRAF3 adaptor molecule deficiency leads to impaired Toll-like receptor 3 response and susceptibility to herpes simplex encephalitis."
Perez de Diego R., Sancho-Shimizu V., Lorenzo L., Puel A., Plancoulaine S., Picard C., Herman M., Cardon A., Durandy A., Bustamante J., Vallabhapurapu S., Bravo J., Warnatz K., Chaix Y., Cascarrigny F., Lebon P., Rozenberg F., Karin M. expand/collapse author list , Tardieu M., Al-Muhsen S., Jouanguy E., Zhang S.Y., Abel L., Casanova J.L.
Immunity 33:400-411(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HSE3 TRP-118.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U15637 mRNA. Translation: AAA56753.1.
U19260 mRNA. Translation: AAA65732.1.
L38509 mRNA. Translation: AAA68195.1.
U21092 mRNA. Translation: AAC50112.1.
BX247977 mRNA. Translation: CAD62311.1.
AK303172 mRNA. Translation: BAH13910.1.
AL117209 Genomic DNA. No translation available.
BC075087 mRNA. Translation: AAH75087.1.
BC075086 mRNA. Translation: AAH75086.1.
AF110908 mRNA. Translation: AAD29276.1.
PIRA55960.
S68467.
RefSeqNP_001186356.1. NM_001199427.1.
NP_003291.2. NM_003300.3.
NP_663777.1. NM_145725.2.
NP_663778.1. NM_145726.2.
UniGeneHs.510528.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1FLKX-ray2.80A/B341-568[»]
1FLLX-ray3.50A/B341-568[»]
1KZZX-ray3.50A377-568[»]
1L0AX-ray2.90A377-568[»]
1RF3X-ray3.50A377-568[»]
1ZMSX-ray2.80A377-568[»]
2ECYNMR-A43-101[»]
2GKWX-ray2.70A377-568[»]
ProteinModelPortalQ13114.
SMRQ13114. Positions 38-257, 364-568.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113039. 97 interactions.
DIPDIP-6222N.
IntActQ13114. 31 interactions.
MINTMINT-1144408.
STRING9606.ENSP00000332468.

PTM databases

PhosphoSiteQ13114.

Polymorphism databases

DMDM116242824.

Proteomic databases

PaxDbQ13114.
PRIDEQ13114.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000392745; ENSP00000376500; ENSG00000131323. [Q13114-1]
ENST00000539721; ENSP00000445998; ENSG00000131323. [Q13114-2]
ENST00000560371; ENSP00000454207; ENSG00000131323. [Q13114-1]
GeneID7187.
KEGGhsa:7187.
UCSCuc001ymc.2. human. [Q13114-1]
uc010txy.2. human. [Q13114-2]

Organism-specific databases

CTD7187.
GeneCardsGC14P103243.
HGNCHGNC:12033. TRAF3.
HPAHPA002933.
MIM601896. gene.
614849. phenotype.
neXtProtNX_Q13114.
Orphanet1930. Herpetic encephalitis.
PharmGKBPA36710.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG239194.
HOVERGENHBG058222.
InParanoidQ13114.
KOK03174.
OMAYGCTFQG.
OrthoDBEOG7966G5.
PhylomeDBQ13114.
TreeFamTF321154.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.
SignaLinkQ13114.

Gene expression databases

ArrayExpressQ13114.
BgeeQ13114.
CleanExHS_CAP1.
HS_TRAF3.
GenevestigatorQ13114.

Family and domain databases

Gene3D3.30.40.10. 1 hit.
3.90.890.10. 1 hit.
InterProIPR002083. MATH.
IPR013323. SIAH-type.
IPR012227. TNF_rcpt--assoc_TRAF.
IPR008974. TRAF-like.
IPR027128. TRAF3.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
IPR001293. Znf_TRAF.
[Graphical view]
PANTHERPTHR10131:SF45. PTHR10131:SF45. 1 hit.
PfamPF00917. MATH. 1 hit.
[Graphical view]
PIRSFPIRSF015614. TRAF. 1 hit.
SMARTSM00061. MATH. 1 hit.
SM00184. RING. 1 hit.
[Graphical view]
SUPFAMSSF49599. SSF49599. 3 hits.
PROSITEPS50144. MATH. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
PS50145. ZF_TRAF. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSTRAF3. human.
EvolutionaryTraceQ13114.
GeneWikiTRAF3.
GenomeRNAi7187.
NextBio28176.
PMAP-CutDBQ13114.
PROQ13114.
SOURCESearch...

Entry information

Entry nameTRAF3_HUMAN
AccessionPrimary (citable) accession number: Q13114
Secondary accession number(s): B7Z8C4 expand/collapse secondary AC list , Q12990, Q13076, Q13947, Q6AZX1, Q9UNL1
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: October 17, 2006
Last modified: April 16, 2014
This is version 164 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 14

Human chromosome 14: entries, gene names and cross-references to MIM