Q13114 (TRAF3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
TNF receptor-associated factor 3

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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	568 AA.
Sequence status	Complete.
Protein existence	Evidence 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. 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.39 Ref.40 Ref.41
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. 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 By similarity. Deubiquitinated by OTUB1, OTUB2 and OTUD5.
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 process	Apoptosis Immunity Ubl conjugation pathway
Cellular component	Cytoplasm Endosome Mitochondrion
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Coiled coil Repeat Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Ligase
PTM	Isopeptide bond Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW induction of apoptosis Traceable author statement. 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 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 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 component	CD40 receptor complex Inferred from sequence or structural similarity. Source: BHF-UCL cytosol Traceable author statement. Source: Reactome endosome Inferred from electronic annotation. Source: UniProtKB-SubCell internal side of plasma membrane Inferred from sequence or structural similarity. Source: BHF-UCL mitochondrion Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	signal transducer activity Traceable author statement. Source: ProtInc ubiquitin-protein ligase activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CD40	P25942	3	EBI-357631,EBI-525714
TANK	Q92844	2	EBI-357631,EBI-356349
TRAF3IP1	Q8TDR0	8	EBI-357631,EBI-928811

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 568

568

TNF receptor-associated factor 3

PRO_0000056401

Regions

Domain

415 – 560

146

MATH

Zinc finger

68 – 77

10

RING-type

Zinc finger

135 – 190

56

TRAF-type 1

Zinc finger

191 – 249

59

TRAF-type 2

Coiled coil

267 – 338

72

Potential

Amino acid modifications

Cross-link

107

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Cross-link

156

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Natural variations

Alternative sequence

191 – 273

83

Missing in isoform 2.

VSP_040040

Natural variant

129

1

M → T. Ref.3 Ref.4
Corresponds to variant rs1131877 [ dbSNP | Ensembl ].

VAR_052149

Experimental info

Mutagenesis

441

1

Y → A: Abolishes interaction with RNF216; when associated with A-443. Ref.31

Mutagenesis

443

1

Q → A: Abolishes interaction with RNF216; when associated with A-441. Ref.31

Mutagenesis

459

1

Y → A: Abolishes interaction with LTBR, CD40 and TANK. Ref.39

Mutagenesis

512

1

F → E: Abolishes interaction with LTBR, CD40 and TANK. Ref.39

Mutagenesis

521

1

F → A: Abolishes interaction with LTBR, CD40 and TANK. Ref.39

Sequence conflict

134

1

Missing in AAA56753. Ref.4

Sequence conflict

158

1

L → F in BAH13910. Ref.6

Sequence conflict

218 – 242

25

Missing in AAA68195. Ref.3

Sequence conflict

339

1

P → S in AAA68195. Ref.3

Sequence conflict

405

1

R → G in AAA56753. Ref.4

Secondary structure

1

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568

Helix Strand Turn

Details...

Turn

54 – 56

3

Beta strand

59 – 62

4

Beta strand

67 – 69

3

Helix

74 – 81

8

Turn

89 – 91

3

Turn

97 – 99

3

Turn

365 – 373

9

Helix

374 – 410

37

Beta strand

414 – 423

10

Helix

425 – 433

9

Beta strand

445 – 448

4

Beta strand

456 – 459

4

Helix

464 – 466

3

Turn

467 – 469

3

Beta strand

470 – 475

6

Turn

481 – 484

4

Beta strand

494 – 498

5

Beta strand

502 – 504

3

Beta strand

508 – 512

5

Beta strand

521 – 523

3

Beta strand

525 – 528

4

Beta strand

533 – 539

7

Helix

540 – 543

4

Beta strand

544 – 546

3

Beta strand

551 – 559

9

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 17, 2006. Version 2. Checksum: 9456E440C0A90FBF	FASTA	568	64,490
	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
	Isoform 2 [UniParc]. Checksum: 1280A3E1B054768D	FASTA	485	55,306
	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 VSLLQNESVE KNKSIQSLHN QICSFEIEIE RQKEMLRNNE SKILHLQRVI 250 260 270 280 290 300 DSQAEKLKEL DKEIRPFRQN WEEADSMKSS VESLQNRVTE LESVDKSAGQ VARNTGLLES 310 320 330 340 350 360 QLSRHDQMLS VHDIRLADMD LRFQVLETAS YNGVLIWKIR DYKRRKQEAV MGKTLSLYSQ 370 380 390 400 410 420 PFYTGYFGYK MCARVYLNGD GMGKGTHLSL FFVIMRGEYD ALLPWPFKQK VTLMLMDQGS 430 440 450 460 470 480 SRRHLGDAFK PDPNSSSFKK PTGEMNIASG CPVFVAQTVL ENGTYIKDDT IFIKVIVDTS DLPDP

References

	« Hide 'large scale' referencesShow '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: 7527023] [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: 7859281] [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: 7530216] [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: 7533327] [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. , 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: 14702039] [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. , 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: 12508121] [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: 15489334] [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: 10199393] [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: 8663299] [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: 8710854] [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: 9168896] [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: 9162022] [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: 9275204] [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: 9718306] [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: 9488716] [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: 9774460] [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: 9774977] [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: 9418902] [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: 10037686] [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: 10523862] [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: 10809768] [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: 10764746] [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: 10791955] [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: 10903733] [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: 11035039] [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: 15383523] [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: 15084608] [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: 17991829] [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: 19419966] [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: 19893624] [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: 19996094] [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: 20097753] [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: 20185819] [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: 19937093] [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: 20174559] [Abstract] Cited for: INTERACTION WITH OPTN AND TBK1.
[37]	"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: 10984535] [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.
[38]	"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: 12005438] [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.
[39]	"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: 14517219] [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.
[40]	"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: 15585864] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 377-568 IN COMPLEX WITH TNFRSF13C PEPTIDE, SUBUNIT, INTERACTION WITH TNFRSF13C.
[41]	"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: 16009714] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 377-568 IN COMPLEX WITH EPSTEIN-BARR VIRUS PROTEIN LMP1, SUBUNIT.
[42]	"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.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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.

IPI

IPI00297473.
IPI00973170.

PIR

A55960.
S68467.

RefSeq

NP_001186356.1. NM_001199427.1.
NP_003291.2. NM_003300.3.
NP_663777.1. NM_145725.2.
NP_663778.1. NM_145726.2.

UniGene

Hs.510528.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1FLK	X-ray	2.80	A/B	341-568	[»]
1FLL	X-ray	3.50	A/B	341-568	[»]
1KZZ	X-ray	3.50	A	377-568	[»]
1L0A	X-ray	2.90	A	377-568	[»]
1RF3	X-ray	3.50	A	377-568	[»]
1ZMS	X-ray	2.80	A	377-568	[»]
2ECY	NMR	-	A	43-101	[»]
2GKW	X-ray	2.70	A	377-568	[»]

ProteinModelPortal

Q13114.

SMR

Q13114. Positions 37-230, 364-568.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-6222N.

IntAct

Q13114. 15 interactions.

MINT

MINT-1144408.

STRING

Q13114.

Polymorphism databases

DMDM

116242824.

Proteomic databases

PRIDE

Q13114.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000351691; ENSP00000332468; ENSG00000131323.
ENST00000392745; ENSP00000376500; ENSG00000131323.

GeneID

7187.

KEGG

hsa:7187.

UCSC

uc001ymc.1. human.

Organism-specific databases

CTD

7187.

GeneCards

GC14P103243.

H-InvDB

HIX0011993.

HGNC

HGNC:12033. TRAF3.

HPA

HPA002933.

MIM

601896. gene.

neXtProt

NX_Q13114.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG18962.

GeneTree

ENSGT00550000074359.

HOGENOM

HBG506127.

HOVERGEN

HBG058222.

InParanoid

Q13114.

OMA

CKSQVPM.

OrthoDB

EOG4JWVD7.

PhylomeDB

Q13114.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

Q13114.

Bgee

Q13114.

CleanEx

HS_CAP1.
HS_TRAF3.

Genevestigator

Q13114.

GermOnline

ENSG00000131323. Homo sapiens.

Family and domain databases

InterPro

IPR002083. MATH.
IPR013323. SIAH-type.
IPR012227. TNF_rcpt--assoc_TRAF.
IPR008974. TRAF-like.
IPR013322. TRAF-type.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
IPR001293. Znf_TRAF.
[Graphical view]

Gene3D

G3DSA:3.90.890.10. SIAH-type. 1 hit.
G3DSA:2.60.210.10. TRAF-type. 1 hit.
G3DSA:3.30.40.10. Znf_RING/FYVE/PHD. 1 hit.

KO

K03174.

Pfam

PF00917. MATH. 1 hit.
[Graphical view]

PIRSF

PIRSF015614. TRAF. 1 hit.

SMART

SM00061. MATH. 1 hit.
SM00184. RING. 1 hit.
[Graphical view]

SUPFAM

SSF49599. Traf_like. 2 hits.

PROSITE

PS50144. MATH. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
PS50145. ZF_TRAF. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

NextBio

28176.

PMAP-CutDB

Q13114.

SOURCE

Search...

Entry information

Entry name

TRAF3_HUMAN

Accession

Primary (citable) accession number: Q13114
Secondary accession number(s): B7Z8C4 , Q12990, Q13076, Q13947, Q6AZX1, Q9UNL1

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	October 17, 2006
Last modified:	January 25, 2012
This is version 141 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.