Skip Header

Contribute Send feedback
Read comments (0) or add your own

Reviewed, UniProtKB/Swiss-Prot Q13114 (TRAF3_HUMAN)

Last modified February 9, 2010. Version 121. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    TNF receptor-associated factor 3
Alternative name(s):
    CD40 receptor-associated factor 1
      Short name=CRAF1
    CD40-binding protein
      Short name=CD40BP
    LMP1-associated protein
    LAP1
    CAP-1
Gene names
Name: TRAF3
Synonyms: CAP1, CRAF1
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

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

General annotation (Comments)

Function

Adapter protein and signal transducer that links members of the tumor necrosis factor receptor family to different signaling pathways by association with the receptor cytoplasmic domain and kinases. Seems to be involved in activation of NF-kappa-B and JNK and in apoptosis. Is regulated by TANK/ITRAF which competes with TNFRSF5/CD40 for binding. Seems to play a role T-cell dependent immune responses.

Subunit structure

Homotrimer Probable. Heteromer with TRAF5 By similarity. Binds to TNFRSF5/CD40. Associates with LTBR/TNFRSF3, TNFRSF4, TNFRSF8/CD30, TNFRSF17/BCMA and EDAR, MAP3K5, MAP3K14, and TRAF-interacting protein TRIP and TRAF and TNF receptor associated protein TTRAP. Binds to TANK/ITRAF and TRAF3IP1. Interacts with TICAM1 By similarity. Interacts with OTUD5. 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

Subcellular location

Cytoplasm Probable.

Domain

The MATH/TRAF domain binds to receptor cytoplasmic domains.

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
   Cellular componentCytoplasm
   Coding sequence diversityPolymorphism
   DomainCoiled coil
Repeat
Zinc-finger
   LigandMetal-binding
Zinc
   Technical term3D-structure
Complete proteome
Gene Ontology (GO)
   Biological processapoptosis

Inferred from electronic annotation. Source: UniProtKB-KW

induction of apoptosis

Traceable author statement. Source: ProtInc

signal transduction Ref.3

Traceable author statement. Source: ProtInc

   Cellular componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular functionprotein binding Ref.4 Ref.18 Ref.21 Ref.29

Inferred from physical interaction. Source: IntAct

signal transducer activity Ref.1 Ref.3

Traceable author statement. Source: ProtInc

zinc ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

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

Natural variations

Natural variant1291M → T: dbSNP rs1131877. Ref.1 Ref.3
VAR_052149

Experimental info

Sequence conflict1341Missing in AAA56753. Ref.4
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
Q13114-1 [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

References

« Hide 'large scale' references
[1]"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], INTERACTION WITH TNFRSF5, VARIANT THR-129.
[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], 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], INTERACTION WITH TNFRSF5, VARIANT THR-129.
Tissue: Fetal brain.
[4]"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], INTERACTION WITH TNFRSF5.
[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].
Tissue: Fetal brain.
[6]"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].
Tissue: Brain.
[7]"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.
[8]"The TNF-receptor-associated factor family: scaffold molecules for cytokine receptors, kinases and their regulators."
Wajant H., Henkler F., Scheurich P.
Cell. Signal. 13:389-400(2001) [PubMed: 11384837] [Abstract]
Cited for: REVIEW.
[9]"Tumor necrosis factor receptor-associated factors (TRAFs)."
Bradley J.R., Pober J.S.
Oncogene 20:6482-6491(2001) [PubMed: 11607847] [Abstract]
Cited for: REVIEW.
[10]"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.
[11]"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.
[12]"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.
[13]"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.
[14]"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.
[15]"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.
[16]"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.
[17]"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.
[18]"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.
[19]"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.
[20]"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.
[21]"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.
[22]"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.
[23]"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.
[24]"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.
[25]"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.
[26]"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.
[27]"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.
[28]"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.
[29]"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.
[30]"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.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U21092 mRNA. Translation: AAC50112.1.
U19260 mRNA. Translation: AAA65732.1.
L38509 mRNA. Translation: AAA68195.1.
U15637 mRNA. Translation: AAA56753.1.
BX247977 mRNA. Translation: CAD62311.1.
BC075087 mRNA. Translation: AAH75087.1.
BC075086 mRNA. Translation: AAH75086.1.
AF110908 mRNA. Translation: AAD29276.1.
IPIIPI00297473.
PIRA55960.
S68467.
RefSeqNP_003291.2.
NP_663777.1.
NP_663778.1.
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[»]
SMRQ13114. Positions 42-139, 136-198, 168-229.
ModBaseSearch...

Protein-protein interaction databases

DIPDIP-6222N.
IntActQ13114. 8 interactions.
STRINGQ13114.

Proteomic databases

PRIDEQ13114.

Genome annotation databases

EnsemblENST00000351691; ENSP00000332468; ENSG00000131323; Homo sapiens. [Genome view]
ENST00000392745; ENSP00000376500; ENSG00000131323; Homo sapiens. [Genome view]
GeneID7187.
KEGGhsa:7187.
UCSCuc001ymc.1. human.

Organism-specific databases

CTD7187.
GeneCardsGC14P102313.
HGNCHGNC:12033. TRAF3.
HPAHPA002933.
MIM601896. gene.
PharmGKBPA36710.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG18962.
HOGENOMHBG506127.
HOVERGENQ13114.
InParanoidQ13114.
OMACKSQVPM.
OrthoDBEOG9DBX00.
PhylomeDBQ13114.

Gene expression databases

ArrayExpressQ13114.
BgeeQ13114.
CleanExHS_CAP1.
HS_TRAF3.
GenevestigatorQ13114.
GermOnlineENSG00000131323. Homo sapiens.

Family and domain databases

InterProIPR002083. MATH.
IPR012227. TNF_recpt_TRAF.
IPR008974. TRAF-like.
IPR013322. TRAF-type.
IPR001841. Znf_RING.
IPR017907. Znf_RING_CS.
IPR001293. Znf_TRAF.
[Graphical view]
Gene3DG3DSA:2.60.210.10. TRAF-type. 1 hit.
PfamPF00917. MATH. 1 hit.
[Graphical view]
PIRSFPIRSF015614. TRAF. 1 hit.
SMARTSM00061. MATH. 1 hit.
SM00184. RING. 1 hit.
[Graphical view]
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 Resources

NextBio28176.
PMAP-CutDBQ13114.
SOURCESearch...

Entry information

Entry nameTRAF3_HUMAN
AccessionPrimary (citable) accession number: Q13114
Secondary accession number(s): Q12990 expand/collapse secondary AC list , Q13076, Q13947, Q6AZX1, Q9UNL1
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: October 17, 2006
Last modified: February 9, 2010
This is version 121 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
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

Human chromosome 14

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

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents