Q9BUZ4 (TRAF4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	470 AA.
Sequence status	Complete.
Protein existence	Evidence 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. Cytoplasm › perinuclear region. Cell junction › tight junction. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Cytoplasm › cytoskeleton 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 process	Apoptosis
Cellular component	Cell junction Cell membrane Cytoplasm Cytoskeleton Membrane Nucleus Tight junction
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Coiled coil Repeat Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Developmental protein
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation of NF-kappaB-inducing kinase activity Inferred from electronic annotation. Source: InterPro apoptotic 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: Compara respiratory tube development Inferred from electronic annotation. Source: Compara signal transduction Traceable author statement Ref.7. Source: ProtInc
Cellular_component	cytoplasm 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_function	DNA binding Traceable author statement Ref.7. 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
Ngfr	P07174	3	EBI-3650647,EBI-1038810	From 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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 470

470

TNF receptor-associated factor 4

PRO_0000056403

Regions

Domain

307 – 462

156

MATH

Zinc finger

18 – 58

41

RING-type

Zinc finger

102 – 154

53

TRAF-type 1

Zinc finger

155 – 208

54

TRAF-type 2

Zinc finger

209 – 266

58

TRAF-type 3

Coiled coil

277 – 309

33

Potential

Amino acid modifications

Modified residue

426

1

Phosphoserine Ref.17 Ref.19

Natural variations

Alternative sequence

157 – 428

272

Missing in isoform 2.

VSP_007403

Natural variant

173

1

A → T. Ref.4
Corresponds to variant rs35932778 [ dbSNP | Ensembl ].

VAR_025805

Natural variant

178

1

R → G. Ref.1
Corresponds to variant rs1044066 [ dbSNP | Ensembl ].

VAR_052150

Secondary structure

1

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470

Helix Strand Turn

Details...

Beta strand

123 – 126

4

Turn

127 – 132

6

Beta strand

142 – 144

3

Helix

150 – 155

6

Turn

156 – 158

3

Beta strand

192 – 194

3

Beta strand

196 – 198

3

Beta strand

201 – 203

3

Helix

204 – 213

10

Beta strand

215 – 220

6

Beta strand

229 – 231

3

Turn

232 – 234

3

Helix

235 – 240

6

Beta strand

243 – 245

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 1, 2001. Version 1. Checksum: A3F57E0E1081AB88	FASTA	470	53,543
	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
	Isoform 2 (TRAF4 variant 5) [UniParc]. Checksum: 1571EDE9630E7398	FASTA	198	22,841
	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 EAYESHESSL GFGYPKFISH QDIRKRNYVR 190 DDAVFIRAAV ELPRKILS

References

	« Hide 'large scale' referencesShow '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. , 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. 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.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

NIEHS-SNPs

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.

IPI

IPI00017037.
IPI00162088.

PIR

I38026.

RefSeq

NP_004286.2. NM_004295.3.

UniGene

Hs.8375.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2EOD	NMR	-	A	190-248	[»]
2YUC	NMR	-	A	101-164	[»]

ProteinModelPortal

Q9BUZ4.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9BUZ4. 5 interactions.

MINT

MINT-107471.

STRING

9606.ENSP00000262395.

PTM databases

PhosphoSite

Q9BUZ4.

Polymorphism databases

DMDM

30580636.

Proteomic databases

PaxDb

Q9BUZ4.

PeptideAtlas

Q9BUZ4.

PRIDE

Q9BUZ4.

Protocols and materials databases

DNASU

9618.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000262395; ENSP00000262395; ENSG00000076604.
ENST00000262396; ENSP00000262396; ENSG00000076604.

GeneID

9618.

KEGG

hsa:9618.

UCSC

uc002hcq.1. human.
uc002hcs.3. human.

Organism-specific databases

CTD

9618.

GeneCards

GC17P027071.

HGNC

HGNC:12034. TRAF4.

HPA

CAB009055.

MIM

602464. gene.

neXtProt

NX_Q9BUZ4.

PharmGKB

PA36711.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG321306.

HOGENOM

HOG000004841.

HOVERGEN

HBG103438.

InParanoid

Q9BUZ4.

KO

K09848.

OMA

EAFESHE.

OrthoDB

EOG4868C9.

Enzyme and pathway databases

SignaLink

Q9BUZ4.

Gene expression databases

ArrayExpress

Q9BUZ4.

Bgee

Q9BUZ4.

CleanEx

HS_TRAF4.

Genevestigator

Q9BUZ4.

GermOnline

ENSG00000076604. Homo sapiens.

Family and domain databases

Gene3D

3.30.40.10. 1 hit.
3.90.890.10. 1 hit.

InterPro

IPR002083. MATH.
IPR013323. SIAH-type.
IPR012227. TNF_rcpt--assoc_TRAF.
IPR008974. TRAF-like.
IPR027138. TRAF4.
IPR018957. Znf_C3HC4_RING-type.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
IPR001293. Znf_TRAF.
[Graphical view]

PANTHER

PTHR10131:SF46. PTHR10131:SF46. 1 hit.

Pfam

PF00917. MATH. 1 hit.
PF00097. zf-C3HC4. 1 hit.
[Graphical view]

PIRSF

PIRSF015614. TRAF. 1 hit.

SMART

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

SUPFAM

SSF49599. Traf_like. 3 hits.

PROSITE

PS50144. MATH. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
PS50145. ZF_TRAF. 3 hits.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

TRAF4. human.

EvolutionaryTrace

Q9BUZ4.

GenomeRNAi

9618.

NextBio

36083.

SOURCE

Search...

Entry information

Entry name

TRAF4_HUMAN

Accession

Primary (citable) accession number: Q9BUZ4
Secondary accession number(s): O75615 , Q14848, Q2KJU4, Q2PJN8

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 9, 2003
Last sequence update:	June 1, 2001
Last modified:	May 29, 2013
This is version 121 of the entry and version 1 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.