Reviewed, UniProtKB/Swiss-Prot P70196 (TRAF6_MOUSE)

Names and origin

Protein names

Recommended name:
    TNF receptor-associated factor 6

Gene names

Name:

Traf6

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	530 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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. Also involved in the IL-1 receptor signaling pathway via MYD88 and IRAK kinases. Seems to be involved in IL-17 signaling. Mediates activation of NF-kappa-B and JNK. May function as an E3 ubiquitin ligase By similarity.
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Homotrimer Probable. Binds to TNFRSF5/CD40 and TNFRSF11A/RANK By similarity. Associates with NGFR, TNFRSF17, IRAK1, IRAK2, IRAK3, IRAK4, PELI1, PELI2, PELI3, RIPK2, MAP3K1, MAP3K5, MAP3K14, CSK, and TRAF-interacting protein TRIP and TRAF and TNF receptor associated protein TTRAP. Binds UBE2V1. Interacts with MAVS/IPS1. Interacts with TAX1BP1 By similarity. Interacts with IL17R. Interacts with SQSTM1 bridging NTRK1 and NGFR. Forms a ternary complex with SQSTM1 and PRKCZ. Interacts with IL1RL1. Interacts with TRAFD1 and JUB By similarity. Interacts with TICAM1 and TICAM2 By similarity.
Subcellular location	Cytoplasm Probable.
Tissue specificity	Highly expressed in brain, lung, liver, skeletal muscle, and kidney; lower expression in heart, spleen, and testis.
Domain	The coiled coil domain mediates homo- and hetero-oligomerization. The MATH/TRAF domain binds to receptor cytoplasmic domains.
Post-translational modification	Polyubiquitinated.
Sequence similarities	Contains 1 MATH domain. Contains 1 RING-type zinc finger. Contains 2 TRAF-type zinc fingers.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing
Domain	Coiled coil Repeat Zinc-finger
Ligand	Metal-binding Zinc
PTM	Ubl conjugation
Gene Ontology (GO)
Biological process	T-helper 1 type immune response Inferred from mutant phenotype. Source: MGI antigen processing and presentation of exogenous peptide antigen via MHC class II Inferred from mutant phenotype. Source: MGI cell development Inferred from mutant phenotype. Source: MGI modification-dependent protein catabolic process Inferred from electronic annotation. Source: UniProtKB-KW myeloid dendritic cell differentiation Inferred from mutant phenotype. Source: MGI neural tube closure Inferred from mutant phenotype. Source: UniProtKB odontogenesis of dentine-containing tooth Inferred from mutant phenotype. Source: MGI ossification Inferred from mutant phenotype. Source: MGI positive regulation of interleukin-12 biosynthetic process Inferred from mutant phenotype. Source: MGI positive regulation of interleukin-6 biosynthetic process Inferred from mutant phenotype. Source: MGI regulation of apoptosis Inferred from electronic annotation. Source: InterPro regulation of immunoglobulin secretion Inferred from direct assay. Source: MGI signal transduction Inferred from direct assay. Source: MGI
Cellular component	cytosol Inferred from direct assay. Source: UniProtKB membrane fraction Inferred from direct assay. Source: UniProtKB
Molecular function	protein binding Ref.1 Inferred from physical interaction. Source: IntAct signal transducer activity Traceable author statement. Source: MGI zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Bat3	Q9Z1R2	2	EBI-448028,EBI-644645
Cd40	P27512	1	EBI-448028,EBI-525742
Ecsit	Q9QZH6	4	EBI-448028,EBI-527020
Irak1	Q62406	1	EBI-448028,EBI-448533
Irak1	Q62406-1	4	EBI-448028,EBI-488313
Map3k3	Q61084	1	EBI-448028,EBI-446250
Rps27a	P62991	1	EBI-448028,EBI-413074
T2bp	Q8R011	1	EBI-448028,EBI-524817
Traf3ip2	Q8C0E5	2	EBI-448028,EBI-530713
Traf3ip2	Q8N7N6	2	EBI-448028,EBI-646165
TRAFD1	O14545	1	EBI-448028,EBI-1396921	From a different organism.
Trafd1	Q3UDK1	1	EBI-448028,EBI-1396948

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P70196-1)

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: P70196-2)

The sequence of this isoform differs from the canonical sequence as follows:
     100-174: DAGHKCPVDN...CQRPFQKCQV → YLILRKHGAL...TQPPGKLQSP
     175-530: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 530	530	TNF receptor-associated factor 6		PRO_0000056408
Regions
	Domain	358 – 507	150	MATH
	Zinc finger	70 – 109	40	RING-type
	Zinc finger	150 – 202	53	TRAF-type 1
	Zinc finger	203 – 259	57	TRAF-type 2
	Region	1 – 362	362	Interaction with TAX1BP1 By similarity
	Coiled coil	299 – 356	58	Potential
Natural variations
	Alternative sequence	100 – 174	75	DAGHK…QKCQV → YLILRKHGALQQPNVKSMLE TGHPKNRQTENTGQEHSRMD RNLRQLGSHPSLYYGMNRGL LPCLPTQPPGKLQSP in isoform 2.		VSP_007404
	Alternative sequence	175 – 530	356	Missing in isoform 2.		VSP_007405

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 1, 1997. Version 1. Checksum: 092D820B4CEDB85B	FASTA	530	60,083
	10 20 30 40 50 60 MSLLNCENSC GSSQSSSDCC AAMAASCSAA VKDDSVSGSA STGNLSSSFM EEIQGYDVEF 70 80 90 100 110 120 DPPLESKYEC PICLMALREA VQTPCGHRFC KACIIKSIRD AGHKCPVDNE ILLENQLFPD 130 140 150 160 170 180 NFAKREILSL TVKCPNKGCL QKMELRHLED HQVHCEFALV NCPQCQRPFQ KCQVNTHIIE 190 200 210 220 230 240 DCPRRQVSCV NCAVSMAYEE KEIHDQSCPL ANIICEYCGT ILIREQMPNH YDLDCPTAPI 250 260 270 280 290 300 PCTFSVFGCH QKMQRNHLAR HLQENTQLHM RLLAQAVHNV NLALRPCDAA SPSRGCRPED 310 320 330 340 350 360 PNYEETIKQL ESRLVRQDHQ IRELTAKMET QSMYVGELKR TIRTLEDKVA EMEAQQCNGI 370 380 390 400 410 420 YIWKIGKFGM HLKSQEEERP VVIHSPGFYT GRPGYKLCMR LHLQLPTAQR CANYISLFVH 430 440 450 460 470 480 TMQGEYDSHL PWPFQGTIRL TILDQSEALI RQNHEEVMDA KPELLAFQRP TIPRNPKGFG 490 500 510 520 530 YVTFMHLEAL RQGTFIKDDT LLVRCEVSTR FDMGGLRKEG FQPRSTDAGV
	Isoform 2. Checksum: F66189179AA9F9D3	FASTA	174	18,961
	10 20 30 40 50 60 MSLLNCENSC GSSQSSSDCC AAMAASCSAA VKDDSVSGSA STGNLSSSFM EEIQGYDVEF 70 80 90 100 110 120 DPPLESKYEC PICLMALREA VQTPCGHRFC KACIIKSIRY LILRKHGALQ QPNVKSMLET 130 140 150 160 170 GHPKNRQTEN TGQEHSRMDR NLRQLGSHPS LYYGMNRGLL PCLPTQPPGK LQSP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of TRAF6, a novel tumor necrosis factor receptor-associated factor protein that mediates signaling from an amino-terminal domain of the CD40 cytoplasmic region." Ishida T., Mizushima S., Azuma S., Kobayashi N., Tojo T., Suzuki K., Aizawa S., Watanabe T., Mosialos G., Kieff E., Yamamoto T., Inoue J. J. Biol. Chem. 271:28745-28748(1996) [PubMed: 8910514] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Strain: C57BL/Kaplan. Tissue: T-cell lymphoma.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Strain: C57BL/6J. Tissue: Aorta and Vein.
[3]	"The atypical PKC-interacting protein p62 channels NF-kappaB activation by the IL-1-TRAF6 pathway." Sanz L., Diaz-Meco M.T., Nakano H., Moscat J. EMBO J. 19:1576-1586(2000) [PubMed: 10747026] [Abstract] Cited for: INTERACTION WITH SQSTM1 AND PRKCZ.
[4]	"Requirement of tumor necrosis factor receptor-associated factor (TRAF)6 in interleukin 17 signal transduction." Schwandner R., Yamaguchi K., Cao Z. J. Exp. Med. 191:1233-1240(2000) [PubMed: 10748240] [Abstract] Cited for: INTERACTION WITH IL17R.
[5]	"The atypical protein kinase C-interacting protein p62 is a scaffold for NF-kappaB activation by nerve growth factor." Wooten M.W., Seibenhener M.L., Mamidipudi V., Diaz-Meco M.T., Barker P.A., Moscat J. J. Biol. Chem. 276:7709-7712(2001) [PubMed: 11244088] [Abstract] Cited for: INTERACTION WITH SQSTM1; PRKCZ AND NGFR.
[6]	"The p62 scaffold regulates nerve growth factor-induced NF-kappaB activation by influencing TRAF6 polyubiquitination." Wooten M.W., Geetha T., Seibenhener M.L., Babu J.R., Diaz-Meco M.T., Moscat J. J. Biol. Chem. 280:35625-35629(2005) [PubMed: 16079148] [Abstract] Cited for: UBIQUITINATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	D84655 mRNA. Translation: BAA12705.1. AK041172 mRNA. Translation: BAC30850.1.
IPI	IPI00136488. IPI00222919.
UniGene	Mm.292729 Mm.460024
3D structure databases
HSSP	HSSP built from PDB template 1LB6 based on UniProtKB Q9Y4K3.
SMR	P70196. Positions 63-124, 355-509.
ModBase	Search...
Protein-protein interaction databases
IntAct	P70196. 17 interactions.
PTM databases
PhosphoSite	P70196.
Proteomic databases
PRIDE	P70196.
Genome annotation databases
Ensembl	ENSMUSG00000027164. Mus musculus. [Contig view]
Organism-specific databases
MGI	MGI:108072. Traf6.
Phylogenomic databases
HOGENOM	P70196.
HOVERGEN	P70196.
Enzyme and pathway databases
Reactome	REACT_11061. Signalling by NGF.
Gene expression databases
ArrayExpress	P70196.
Bgee	P70196.
CleanEx	MM_TRAF6.
GermOnline	ENSMUSG00000027164. Mus musculus.
Family and domain databases
InterPro	IPR002083. MATH. IPR012227. TNF_recpt_TRAF. IPR013322. TRAF-type. IPR018957. Znf_C3HC4_RING-type. IPR001841. Znf_RING. IPR017907. Znf_RING_CS. IPR001293. Znf_TRAF. [Graphical view]
Gene3D	G3DSA:2.60.210.10. TRAF-type. 1 hit.
Pfam	PF00917. MATH. 1 hit. PF00097. zf-C3HC4. 1 hit. PF02176. zf-TRAF. 2 hits. [Graphical view]
PIRSF	PIRSF015614. TRAF. 1 hit.
SMART	SM00061. MATH. 1 hit. SM00184. RING. 1 hit. [Graphical view]
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 Resources
SOURCE	Search...

Entry information

Entry name

TRAF6_MOUSE

Accession

Primary (citable) accession number: P70196
Secondary accession number(s): Q8BLV2

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 9, 2003
Last sequence update:	February 1, 1997
Last modified:	June 16, 2009
This is version 92 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)