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Q9BUZ4 (TRAF4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 128. 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 4
Alternative name(s):
Cysteine-rich domain associated with RING and Traf domains protein 1
Metastatic lymph node gene 62 protein
Short name=MLN 62
RING finger protein 83
Gene names
Name:TRAF4
Synonyms:CART1, MLN62, RNF83
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length470 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 (TNFR) family to different signaling pathways. Plays a role in the activation of NF-kappa-B and JNK, and in the regulation of cell survival and apoptosis. Regulates activation of NF-kappa-B in response to signaling through Toll-like receptors. Required for normal skeleton development, and for normal development of the respiratory tract By similarity. Required for activation of RPS6KB1 in response to TNF signaling. Modulates TRAF6 functions. Ref.10 Ref.11 Ref.12 Ref.13 Ref.16 Ref.18

Subunit structure

Homotrimer Probable. Interacts with LTBR/TNFRSF3, NGFR/TNFRSF16, RPS6KB1 and TGFB1I1. Interacts with SMURF1. Interacts (via TRAF domain) with MAP3K4 (via kinase domain). Interacts with NCF1, TICAM1, IRAK1 and TRAF6, and is probably part of a complex containing TRAF4, NCF1, TICAM1, IRAK1 and TRAF6. Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.18

Subcellular location

Cytoplasm. Nucleus. Cytoplasmperinuclear region. Cell junctiontight junction. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Cytoplasmcytoskeleton Probable Ref.7 Ref.8 Ref.10 Ref.13 Ref.15 Ref.16.

Tissue specificity

Expressed in epithelial cells of thymus, dendritic cells of lymph node, and in the basal cell layer of epithelia such as epidermis, nasopharynx, respiratory tract, salivary gland, and esophagus. Ref.7 Ref.8

Induction

Up-regulated by bacterial lipopolysaccharides (LPS) and by single-stranded CpG oligodeoxynucleotide. Ref.12

Domain

The coiled coil domain mediates homo- and hetero-oligomerization By similarity.

The MATH/TRAF domain binds to receptor cytoplasmic domains By similarity.

Post-translational modification

Polyubiquitinated, leading to its proteasomal degradation.

Sequence similarities

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

Contains 1 MATH domain.

Contains 1 RING-type zinc finger.

Contains 3 TRAF-type zinc fingers.

Ontologies

Keywords
   Biological processApoptosis
   Cellular componentCell junction
Cell membrane
Cytoplasm
Cytoskeleton
Membrane
Nucleus
Tight junction
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainCoiled coil
Repeat
Zinc-finger
   LigandMetal-binding
Zinc
   Molecular functionDevelopmental protein
   PTMPhosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processapoptotic process

Inferred from electronic annotation. Source: UniProtKB-KW

positive regulation of JNK cascade

Inferred from direct assay Ref.13. Source: UniProtKB

positive regulation of protein homodimerization activity

Inferred from direct assay Ref.13. Source: UniProtKB

positive regulation of protein kinase activity

Inferred from direct assay Ref.13. Source: UniProtKB

regulation of apoptotic process

Inferred from electronic annotation. Source: InterPro

respiratory gaseous exchange

Inferred from electronic annotation. Source: Ensembl

respiratory tube development

Inferred from electronic annotation. Source: Ensembl

signal transduction

Traceable author statement Ref.7. Source: ProtInc

   Cellular_componentcytoplasm

Inferred from direct assay Ref.13. Source: UniProtKB

cytoskeleton

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from direct assay Ref.15. Source: UniProtKB

perinuclear region of cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

tight junction

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionDNA binding

Traceable author statement Ref.7. Source: ProtInc

WW domain binding

Inferred from physical interaction Ref.18. Source: UniProtKB

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

With

Entry

#Exp.

IntAct

Notes

NgfrP071743EBI-3650647,EBI-1038810From a different organism.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9BUZ4-1)

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: Q9BUZ4-2)

Also known as: TRAF4 variant 5;

The sequence of this isoform differs from the canonical sequence as follows:
     157-428: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 470470TNF receptor-associated factor 4
PRO_0000056403

Regions

Domain307 – 462156MATH
Zinc finger18 – 5841RING-type
Zinc finger102 – 15453TRAF-type 1
Zinc finger155 – 20854TRAF-type 2
Zinc finger209 – 26658TRAF-type 3
Coiled coil277 – 30933 Potential

Amino acid modifications

Modified residue4261Phosphoserine Ref.17 Ref.19

Natural variations

Alternative sequence157 – 428272Missing in isoform 2.
VSP_007403
Natural variant1731A → T. Ref.4
Corresponds to variant rs35932778 [ dbSNP | Ensembl ].
VAR_025805
Natural variant1781R → G. Ref.1
Corresponds to variant rs1044066 [ dbSNP | Ensembl ].
VAR_052150

Secondary structure

...................................................... 470
Helix Strand Turn

Details...

Sequences

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

Last modified June 1, 2001. Version 1.
Checksum: A3F57E0E1081AB88

FASTA47053,543
        10         20         30         40         50         60 
MPGFDYKFLE KPKRRLLCPL CGKPMREPVQ VSTCGHRFCD TCLQEFLSEG VFKCPEDQLP 

        70         80         90        100        110        120 
LDYAKIYPDP ELEVQVLGLP IRCIHSEEGC RWSGPLRHLQ GHLNTCSFNV IPCPNRCPMK 

       130        140        150        160        170        180 
LSRRDLPAHL QHDCPKRRLK CEFCGCDFSG EAYESHEGMC PQESVYCENK CGARMMRRLL 

       190        200        210        220        230        240 
AQHATSECPK RTQPCTYCTK EFVFDTIQSH QYQCPRLPVA CPNQCGVGTV AREDLPGHLK 

       250        260        270        280        290        300 
DSCNTALVLC PFKDSGCKHR CPKLAMARHV EESVKPHLAM MCALVSRQRQ ELQELRRELE 

       310        320        330        340        350        360 
ELSVGSDGVL IWKIGSYGRR LQEAKAKPNL ECFSPAFYTH KYGYKLQVSA FLNGNGSGEG 

       370        380        390        400        410        420 
THLSLYIRVL PGAFDNLLEW PFARRVTFSL LDQSDPGLAK PQHVTETFHP DPNWKNFQKP 

       430        440        450        460        470 
GTWRGSLDES SLGFGYPKFI SHQDIRKRNY VRDDAVFIRA AVELPRKILS 

« Hide

Isoform 2 (TRAF4 variant 5) [UniParc].

Checksum: 1571EDE9630E7398
Show »

FASTA19822,841

References

« Hide 'large scale' references
[1]"Identification of four novel human genes amplified and overexpressed in breast carcinoma and localized to the q11-q21.3 region of chromosome 17."
Tomasetto C.L., Regnier C.H., Moog-Lutz C., Mattei M.-G., Chenard M.-P., Lidereau R., Basset P., Rio M.-C.
Genomics 28:367-376(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT GLY-178.
Tissue: Mammary tumor.
[2]"TRAF4 expression in proliferating cells."
Miller H.G., Pullen S.P., White H.E., Phipps R.P., Kehry M.R., Crute J.J.
Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Tissue: Lung.
[3]Cai C.L., Li R., Wang R.S., Miao S.Y., Wang L.F.
Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Cervix carcinoma.
[4]NIEHS SNPs program
Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT THR-173.
[5]"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. expand/collapse author list , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Retinoblastoma.
[7]"Presence of a new conserved domain in CART1, a novel member of the tumor necrosis factor receptor-associated protein family, which is expressed in breast carcinoma."
Regnier C.H., Tomasetto C., Moog-Lutz C., Chenard M.-P., Wendling C., Basset P., Rio M.-C.
J. Biol. Chem. 270:25715-25721(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[8]"TRAF-4 expression in epithelial progenitor cells. Analysis in normal adult, fetal, and tumor tissues."
Krajewska M., Krajewski S., Zapata J.M., VanArsdale T., Gascoyne R.D., Berern K., McFadden D., Shabaik A., Hugh J., Reynolds A., Clevenger C.V., Reed J.C.
Am. J. Pathol. 152:1549-1561(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH LTBR AND TNFRSDF16, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[9]"TRAF family proteins interact with the common neurotrophin receptor and modulate apoptosis induction."
Ye X., Mehlen P., Rabizadeh S., VanArsdale T., Zhang H., Shin H., Wang J.J.L., Leo E., Zapata J.M., Hauser C.A., Reed J.C., Bredesen D.E.
J. Biol. Chem. 274:30202-30208(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TNFRSF16.
[10]"Involvement of TRAF4 in oxidative activation of c-Jun N-terminal kinase."
Xu Y.C., Wu R.F., Gu Y., Yang Y.S., Yang M.C., Nwariaku F.E., Terada L.S.
J. Biol. Chem. 277:28051-28057(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH NCF1, SUBCELLULAR LOCATION.
[11]"Tumor necrosis factor receptor-associated factor (TRAF) 4 is a new binding partner for the p70S6 serine/threonine kinase."
Fleckenstein D.S., Dirks W.G., Drexler H.G., Quentmeier H.
Leuk. Res. 27:687-694(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH RPS6KB1.
[12]"TRAF4 acts as a silencer in TLR-mediated signaling through the association with TRAF6 and TRIF."
Takeshita F., Ishii K.J., Kobiyama K., Kojima Y., Coban C., Sasaki S., Ishii N., Klinman D.M., Okuda K., Akira S., Suzuki K.
Eur. J. Immunol. 35:2477-2485(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH NCF1; TICAM1; IRAK1 AND TRAF6, INDUCTION.
[13]"MEKK4 is an effector of the embryonic TRAF4 for JNK activation."
Abell A.N., Johnson G.L.
J. Biol. Chem. 280:35793-35796(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH MAP3K4.
[14]"Subcellular targeting of oxidants during endothelial cell migration."
Wu R.F., Xu Y.C., Ma Z., Nwariaku F.E., Sarosi G.A. Jr., Terada L.S.
J. Cell Biol. 171:893-904(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TGFB1I1.
[15]"TRAF4 is potently induced by TAp63 isoforms and localised according to differentiation in SCCHN."
Gu X., Coates P.J., MacCallum S.F., Boldrup L., Sjostrom B., Nylander K.
Cancer Biol. Ther. 6:1986-1990(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[16]"Tumor necrosis factor receptor-associated factor 4 is a dynamic tight junction-related shuttle protein involved in epithelium homeostasis."
Kedinger V., Alpy F., Baguet A., Polette M., Stoll I., Chenard M.P., Tomasetto C., Rio M.C.
PLoS ONE 3:E3518-E3518(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[17]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-426, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[18]"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: FUNCTION, INTERACTION WITH SMURF1, UBIQUITINATION.
[19]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-426, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[20]"Solution structure of TRAF-type zinc finger domains from human TNF receptor-associated factor 4."
RIKEN structural genomics initiative (RSGI)
Submitted (APR-2008) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 101-248.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X80200 mRNA. Translation: CAA56491.1.
AF082185 mRNA. Translation: AAC32376.1.
AY937224 mRNA. Translation: AAY16990.1.
DQ323999 Genomic DNA. Translation: ABC40750.1.
AC010761 Genomic DNA. No translation available.
BC001769 mRNA. Translation: AAH01769.1.
PIRI38026.
RefSeqNP_004286.2. NM_004295.3.
UniGeneHs.8375.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2EODNMR-A190-248[»]
2YUCNMR-A101-164[»]
3ZJBX-ray1.84A/B/C283-470[»]
4K8UX-ray2.30A/B/C281-470[»]
4M4EX-ray2.60A/B/C292-466[»]
ProteinModelPortalQ9BUZ4.
SMRQ9BUZ4. Positions 3-248, 298-465.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114979. 48 interactions.
DIPDIP-40910N.
IntActQ9BUZ4. 12 interactions.
MINTMINT-107471.
STRING9606.ENSP00000262395.

PTM databases

PhosphoSiteQ9BUZ4.

Polymorphism databases

DMDM30580636.

Proteomic databases

PaxDbQ9BUZ4.
PeptideAtlasQ9BUZ4.
PRIDEQ9BUZ4.

Protocols and materials databases

DNASU9618.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000262395; ENSP00000262395; ENSG00000076604. [Q9BUZ4-1]
ENST00000262396; ENSP00000262396; ENSG00000076604.
GeneID9618.
KEGGhsa:9618.
UCSCuc002hcq.1. human. [Q9BUZ4-2]
uc002hcs.3. human. [Q9BUZ4-1]

Organism-specific databases

CTD9618.
GeneCardsGC17P027071.
HGNCHGNC:12034. TRAF4.
HPACAB009055.
HPA052377.
MIM602464. gene.
neXtProtNX_Q9BUZ4.
PharmGKBPA36711.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG321306.
HOGENOMHOG000004841.
HOVERGENHBG103438.
InParanoidQ9BUZ4.
KOK09848.
OMAEAFESHE.
OrthoDBEOG7966G5.
PhylomeDBQ9BUZ4.
TreeFamTF321154.

Enzyme and pathway databases

SignaLinkQ9BUZ4.

Gene expression databases

ArrayExpressQ9BUZ4.
BgeeQ9BUZ4.
CleanExHS_TRAF4.
GenevestigatorQ9BUZ4.

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.
IPR018957. Znf_C3HC4_RING-type.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
IPR001293. Znf_TRAF.
[Graphical view]
PfamPF00917. MATH. 1 hit.
PF00097. zf-C3HC4. 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. 3 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSTRAF4. human.
EvolutionaryTraceQ9BUZ4.
GeneWikiTRAF4.
GenomeRNAi9618.
NextBio36083.
PROQ9BUZ4.
SOURCESearch...

Entry information

Entry nameTRAF4_HUMAN
AccessionPrimary (citable) accession number: Q9BUZ4
Secondary accession number(s): O75615 expand/collapse secondary AC list , Q14848, Q2KJU4, Q2PJN8
Entry history
Integrated into UniProtKB/Swiss-Prot: May 9, 2003
Last sequence update: June 1, 2001
Last modified: April 16, 2014
This is version 128 of the entry and version 1 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 17

Human chromosome 17: entries, gene names and cross-references to MIM